Skip to main content
SpringerLink
Log in
Book cover

Cholesterol Binding and Cholesterol Transport Proteins: pp 509–549Cite as

Cholesterol and Ion Channels

  • Chapter
  • First Online:

Part of the book series: Subcellular Biochemistry ((SCBI,volume 51))

Abstract

A variety of ion channels, including members of all major ion channel families, have been shown to be regulated by changes in the level of membrane cholesterol and partition into cholesterol-rich membrane domains. In general, several types of cholesterol effects have been described. The most common effect is suppression of channel activity by an increase in membrane cholesterol, an effect that was described for several types of inwardly-rectifying K+ channels, voltage-gated K+ channels, Ca+2 sensitive K+ channels, voltage-gated Na+ channels, N-type voltage-gated Ca+2 channels and volume-regulated anion channels. In contrast, several types of ion channels, such as epithelial amiloride-sensitive Na+ channels and Transient Receptor Potential channels, as well as some of the types of inwardly-rectifying and voltage-gated K+ channels were shown to be inhibited by cholesterol depletion. Cholesterol was also shown to alter the kinetic properties and current-voltage dependence of several voltage-gated channels. Finally, maintaining membrane cholesterol level is required for coupling ion channels to signalling cascades. In terms of the mechanisms, three general mechanisms have been proposed: (i) specific interactions between cholesterol and the channel protein, (ii) changes in the physical properties of the membrane bilayer and (iii) maintaining the scaffolds for protein-protein interactions. The goal of this review is to describe systematically the role of cholesterol in regulation of the major types of ion channels and to discuss these effects in the context of the models proposed.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abi-Char, J.l., Maguy, A., Coulombe, A., Balse, E., Ratajczak, P., Samuel, J.-L., Nattel, S., and Hatem, S.p.N., 2007, Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes. The Journal of Physiology 582: 1205.

    Article  CAS  PubMed  Google Scholar 

  • Absi, M., Burnham, M.P., Weston, A.H., Harno, E., Rogers, M., and Edwards, G., 2007, Effects of methyl beta-cyclodextrin on EDHF responses in pig and rat arteries; association between SK(Ca) channels and caveolin-rich domains. Br J Pharmacol. 151: 332–40.

    Google Scholar 

  • Allen, J.A., Halverson-Tamboli, R.A., and Rasenick, M.M., 2007, Lipid raft microdomains and neurotransmitter signalling. Nat Rev Neurosci 8: 128–140.

    Article  CAS  PubMed  Google Scholar 

  • Babiychuk, E.B., Smith, R.D., Burdyga, T., Babiychuk, V.S., Wray, S., and Draeger, A., 2004, Membrane cholesterol regulates smooth muscle phasic contraction. J Membr Biol 198: 95–101.

    Article  CAS  PubMed  Google Scholar 

  • Balijepalli, R.C., Foell, J.D., Hall, D.D., Hell, J.W., and Kamp, T.J., 2006, Localization of cardiac L-type Ca2+ channels to a caveolar macromolecular signalling complex is required for beta2-adrenergic regulation. PNAS 103: 7500–7505.

    Article  CAS  PubMed  Google Scholar 

  • Balijepalli, R.C., and Kamp, T.J., 2008, Caveolae, ion channels and cardiac arrhythmias. Progress in Biophysics and Molecular Biology 98: 149.

    Article  CAS  PubMed  Google Scholar 

  • Balut, C., Steels, P., Radu, M., Ameloot, M., Driessche, W.V., and Jans, D., 2006, Membrane cholesterol extraction decreases Na+ transport in A6 renal epithelia. Am J Physiol Cell Physiol 290: C87–94.

    Article  CAS  PubMed  Google Scholar 

  • Barrantes, F.J., 2004, Structural basis for lipid modulatioon of nicotinic acetylcholine receptor function. Brain Research Reviews 47: 71–95.

    Article  CAS  PubMed  Google Scholar 

  • Beech, D.J., 2005, TRPC1: store-operated channel and more. Pflugers Arch. 451: 53–60.

    Article  CAS  PubMed  Google Scholar 

  • Beech, D.J, Bahnasi, Y.M., Dedman, A.M., and Al-Shawaf, E., 2009, TRPC channel lipid specificity and mechanisms of lipid regulation. Cell Calcium 45: 583–8.

    Article  CAS  PubMed  Google Scholar 

  • Begenisich, T., Nakamoto, T., Ovitt, C.E., Nehrke, K., Brugnara, C., Alper, S.L., and Melvin, J.E., 2004, Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4. J Biol Chem 279: 47681–47687.

    Article  CAS  PubMed  Google Scholar 

  • Berdiev, B.K., Qadri, Y.J., and Benos, D.J., 2009, Assessment of the CFTR and ENaC association. Mol Biosyst 5: 123–127.

    Article  CAS  PubMed  Google Scholar 

  • Bergdahl, A., Gomez, M.F., Dreja, K., Xu, S.Z., Adner, M., Beech, D.J., Broman, J., Hellstrand, P., and Swärd, K., 2003, Cholesterol depletion impairs vascular reactivity to endothelin-1 by reducing store-operated Ca2+ entry dependent on TRPC1. Circ. Res. 93: 839–47.

    Article  CAS  PubMed  Google Scholar 

  • Berthier, A., Lemaire-Ewing, S., Prunet, C., Monier, S., Athias, A., Bessède, G., Pais de Barros, J.P., Laubriet, A., Gambert, P., Lizard, G., and Néel, D., 2004, Involvement of a calcium-dependent dephosphorylation of BAD associated with the localization of Trpc-1 within lipid rafts in 7-ketocholesterol-induced THP-1 cell apoptosis. Cell Death Differ. 11: 897–905.

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharjee, A., and Kaczmarek, L.K., 2005, For K+ channels, Na+ is the new Ca2+. Trends Neurosci 28: 422–428.

    Article  CAS  PubMed  Google Scholar 

  • Bichet, D., Haass, F.A., and Jan, L.Y., 2003, Merging functional studies with structures of inward-rectifier K(+) channels. Nat Rev Neurosci. 4: 957–967.

    Article  CAS  PubMed  Google Scholar 

  • Bock, J., Szabo, I., Gamper, N., Adams, C., and Gulbins, E., 2003, Ceramide inhibits the potassium channel Kv1.3 by the formation of membrane platforms. Biochemical and Biophysical Research Communications 305: 890.

    Article  CAS  PubMed  Google Scholar 

  • Bolotina, V., Omelyanenko, V., Heyes, B., Ryan, U., and Bregestovski, P., 1989, Variations of membrane cholesterol alter the kinetics of Ca2+-dependent K+ channels and membrane fluidity in vascular smooth muscle cells. Pflugers Archives 415: 262–268.

    Article  CAS  Google Scholar 

  • Bond, C.T., Maylie, J., and Adelman, J.P., 1999, Small-conductance calcium-activated potassium channels. Ann N Y Acad Sci 868: 370–378.

    Article  CAS  PubMed  Google Scholar 

  • Bond, C.T., Maylie, J., and Adelman, J.P., 2005, SK channels in excitability, pacemaking and synaptic integration. Curr Opin Neurobiol 15: 305–311.

    Article  CAS  PubMed  Google Scholar 

  • Bowles, D.K., Heaps, C.L., Turk, J.R., Maddali, K.K., and Price, E.M., 2004, Hypercholesterolemia inhibits L-type calcium current in coronary macro-, not microcirculation. J. Appl. Physiol. 96: 2240–2248.

    Article  CAS  PubMed  Google Scholar 

  • Brainard, A.M., Miller, A.J., Martens, J.R., and England, S.K., 2005, Maxi-K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K+ current. Am. J. Physiol. Cell Physiol. 289: C49–57.

    Article  CAS  PubMed  Google Scholar 

  • Bravo-Zehnder, M., Orio, P., Norambuena, A., Wallner, M., Meera, P., Toro, L., Latorre, R., and Gonzalez, A., 2000, Apical sorting of a voltage- and Ca2+-activated K+ channel alpha -subunit in Madin-Darby canine kidney cells is independent of N-glycosylation. Proc. Natl. Acad. Sci. U.S.A. 97: 13114–13119.

    Article  CAS  PubMed  Google Scholar 

  • Brazer, S.C., Singh, B.B., Liu, X., Swaim, W., and Ambudkar, I.S., 2003, Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1. J. Biol. Chem. 278: 27208–15.

    Article  CAS  PubMed  Google Scholar 

  • Brownlow, S.L., Harper, A.G., Harper, M.T., and Sage, S.O., 2004, A role for hTRPC1 and lipid raft domains in store-mediated calcium entry in human platelets. Cell Calcium 35: 107–13.

    Article  CAS  PubMed  Google Scholar 

  • Brownlow, S.L., and Sage, S.O., 2005, Transient receptor potential protein subunit assembly and membrane distribution in human platelets. Thromb. Haemost. 94: 839–45.

    PubMed  Google Scholar 

  • Byfield, F.J., Aranda-Espinoza, H., Romanenko, V.G., Rothblat, G.H., and Levitan, I., 2004, Cholesterol depletion increases membrane stiffness of aortic endothelial cells. Biophys. J. 87: 3336–3343.

    Article  CAS  PubMed  Google Scholar 

  • Byfield, F.J., Hoffman, B.D., Romanenko, V.G., Fang, Y., Crocker, J.C., and Levitan, I., 2006, Evidence for the role of cell stiffness in modulation of volume-regulated anion channels. Acta Physiol. 187: 285–294.

    Article  CAS  Google Scholar 

  • Catterall, W.A., Goldin, A.L., and Waxman, S.G., 2005a, International Union of Pharmacology. XLVII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels. Pharmacol. Rev. 57: 397–409.

    Article  CAS  PubMed  Google Scholar 

  • Catterall, W.A., Perez-Reyes, E., Snutch, T.P., and Striessnig, J., 2005b, International Union of Pharmacology. XLVIII. Nomenclature and Structure-Function Relationships of Voltage-Gated Calcium Channels. Pharmacol. Rev. 57: 411–425.

    Article  CAS  PubMed  Google Scholar 

  • Chang, H.M., Reitstetter, R., Mason, R.P., and Gruener, R., 1995, Attenuation of channel kinetics and conductance by cholesterol: an interpretation using structural stress as a unifying concept. J. Membrane Biol. 143: 51–63.

    Article  CAS  Google Scholar 

  • Cheema, T.A., and Fisher, S.K., 2008, Cholesterol regulates volume-sensitive osmolyte efflux from human SH-SY5Y neuroblastoma cells following receptor activation. J. Pharmacol. Exp. Ther. 324: 648–657.

    Article  CAS  PubMed  Google Scholar 

  • Cheng, S.H., Gregory, R.J., Marshall, J., Paul, S., Souza, D.W., White, G.A., O’Riordan, C.R., and Smith, A.E., 1990, Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 63: 827–834.

    Article  CAS  PubMed  Google Scholar 

  • Cho, W.J., Jeremic, A., Jin, H., Ren, G., and Jena, B.P., 2007, Neuronal fusion pore assembly requires membrane cholesterol. Cell Biol. Int. 31: 1301–1308.

    Article  CAS  PubMed  Google Scholar 

  • Christenson, E., Merlin, S., Saito, M., and Schlesinger, P., 2008, Cholesterol effects on BAX pore activation. J. Mol. Biol. 381: 1168–1183.

    Article  CAS  PubMed  Google Scholar 

  • Clapham, D.E., 2003, TRP channels as cellular sensors. Nature 426: 517–24.

    Article  CAS  PubMed  Google Scholar 

  • Cox, R.H., and Tulenko, T.N., 1995, Altered contractile and ion channel function in rabbit portal vein with dietary atherosclerosis. Am. J. Physiol. 268: H2522–2530.

    CAS  PubMed  Google Scholar 

  • Criado, M., Eibl, H., and Barrantes, F.J., 1982, Effects of lipids on acetylcholine receptor. Essential need of cholesterol for maintenance of agonist-induced state transitions in lipid vesicles. Biochemistry 21: 3622–3629.

    Article  CAS  PubMed  Google Scholar 

  • Crowley, J.J., Treistman, S.N., and Dopico, A.M., 2003, Cholesterol antagonizes ethanol potentiation of human brain BKCa channels reconstituted into phospholipid bilayers. Mol. Pharmacol. 64: 365–372.

    Article  CAS  PubMed  Google Scholar 

  • Davies, P.F., 1995, Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75: 519–560.

    CAS  PubMed  Google Scholar 

  • de la Rosa, D.A., Canessa, C.M., Fyfe, G.K., and Zhang, P., 2000, Structure and Regulation of Amiloride-Sensitive Sodium Channels. Ann. Rev. Physiol. 62: 573.

    Article  Google Scholar 

  • De Pinto, V., Benz, R., Caggese, C., and Palmieri, F., 1989, Characterization of the mitochondrial porin from Drosophila melanogaster. Biochim. Biophys. Acta 987: 1–7.

    Article  PubMed  Google Scholar 

  • Delling, M., Wischmeyer, E., Dityatev, A., Sytnyk, V., Veh, R.W., Karschin, A., and Schachner, M., 2002, The Neural Cell Adhesion Molecule Regulates Cell-Surface Delivery of G-Protein-Activated Inwardly Rectifying Potassium Channels Via Lipid Rafts. J. Neurosci. 22: 7154–7164.

    CAS  PubMed  Google Scholar 

  • Delmas, P., 2004, Assembly and gating of TRPC channels in signalling microdomains. Novartis Found. Symp. 258: 75–89; discussion 89–102, 263–6.

    Article  CAS  PubMed  Google Scholar 

  • Demel, R.A., Bruckdorfer, K.R., and van Deenen, L.L.M., 1972, Structural requrements of sterols for the interaction with lecithin at the air-water interface. Biochem. Biophys. Acta 255: 311–320.

    Article  CAS  PubMed  Google Scholar 

  • Du, P., Cui, G.B., Wang, Y.R., Zhang, X.Y., Ma, K.J., and Wei, J.G., 2006, Down regulated expression of the beta1 subunit of the big-conductance Ca2+ sensitive K+ channel in sphincter of Oddi cells from rabbits fed with a high cholesterol diet. Acta Biochim. Biophys. Sin. (Shanghai). 38: 893–899.

    Article  CAS  Google Scholar 

  • Dudez, T., Borot, F., Huang, S., Kwak, B.R., Bacchetta, M., Ollero, M., Stanton, B.A., and Chanson, M., 2008, CFTR in a lipid raft-TNFR1 complex modulates gap junctional intercellular communication and IL-8 secretion. Biochim. Biophys. Acta 1783: 779–788.

    Article  CAS  PubMed  Google Scholar 

  • Edwards, G., and Weston, A.H., 1993, The Pharmacology of ATP-Sensitive Potassium Channels. Ann. Rev. Pharmacol. Toxicol. 33: 597–637.

    Article  CAS  Google Scholar 

  • Eldstrom, J., Van Wagoner, D.R., Moore, E.D., and Fedida, D., 2006, Localization of Kv1.5 channels in rat and canine myocyte sarcolemma. FEBS Lett. 580: 6039.

    Article  CAS  PubMed  Google Scholar 

  • Epshtein, Y., Chopra, A., Rosenhouse-Dantsker, A., Kowalsky, G., D.E., L., and Levitan, I., 2009, Identification of a C-terminus domain critical for the sensitivity of Kir2.1 channels to cholesterol. Proc. Natl. Acad. Sci. U.S.A. 106: 8055–8060.

    Google Scholar 

  • Fang, Y., Mohler, E.R., III, Hsieh, E., Osman, H., Hashemi, S.M., Davies, P.F., Rothblat, G.H., Wilensky, R.L., and Levitan, I., 2006, Hypercholesterolemia suppresses inwardly rectifying k+ channels in aortic endothelium in vitro and in vivo. Circ. Res. 98: 1064–1071.

    Article  CAS  PubMed  Google Scholar 

  • Fang, Y., Schram, G., Romanenko, V.G., Shi, C., Conti, L., Vandenberg, C.A., Davies, P.F., Nattel, S., and Levitan, I., 2005, Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2. Am. J. Physiol. Cell Physiol. 289: C1134–1144.

    Article  CAS  PubMed  Google Scholar 

  • Feletou, M., 2009, Calcium-activated potassium channels and endothelial dysfunction: therapeutic options? Br. J. Pharmacol. 156: 545–562.

    Article  CAS  PubMed  Google Scholar 

  • Formigli, L., Sassoli, C., Squecco, R., Bini, F., Martinesi, M., Chellini, F., Luciani, G., Sbrana, F., Zecchi-Orlandini, S., Francini, F., and Meacci, E., 2009, Regulation of transient receptor potential canonical channel 1 (TRPC1) by sphingosine 1-phosphate in C2C12 myoblasts and its relevance for a role of mechanotransduction in skeletal muscle differentiation. J. Cell Sci. 122: 1322–33.

    Article  CAS  PubMed  Google Scholar 

  • Foster, L.J., and Chan, Q.W., 2007, Lipid raft proteomics: more than just detergent-resistant membranes. Subcell Biochem. 43: 35–47.

    Article  PubMed  Google Scholar 

  • Freitag, H., Genchi, G., Benz, R., Palmieri, F., and Neupert, W., 1982, Isolation of mitochondrial porin from Neurospora crassa. FEBS Lett. 145: 72–76.

    Article  CAS  PubMed  Google Scholar 

  • Garofalo, T., Giammarioli, A.M., Misasi, R., Tinari, A., Manganelli, V., Gambardella, L., Pavan, A., Malorni, W., and Sorice, M., 2005, Lipid microdomains contribute to apoptosis-associated modifications of mitochondria in T cells. Cell Death Differ. 12: 1378–1389.

    Article  CAS  PubMed  Google Scholar 

  • Gasque, Labarca, and Darszon. 2005, Cholesterol-depleting compounds modulate K+-currents in Drosophila Kenyon cells. FEBS Lett. 579: 5129.

    Article  CAS  PubMed  Google Scholar 

  • Genda, S., Miura, T., Miki, T., Ichikawa, Y., and Shimamoto K., 2002, K(ATP) channel opening is an endogenous mechanism of protection against the no-reflow phenomenon but its function is compromised by hypercholesterolemia. J Am Coll Cardiol. 40: 1339–1346.

    Google Scholar 

  • Ghanam, K., Javellaud, J., Ea-Kim, L., and Oudart, N., 2000, Effects of treatment with 17beta-estradiol on the hypercholesterolemic rabbit middle cerebral artery. Maturitas 34: 249–260.

    Article  CAS  PubMed  Google Scholar 

  • Ghanshani, S., Wulff, H., Miller, M.J., Rohm, H., Neben, A., Gutman, G.A., Cahalan, M.D., and Chandy, K.G., 2000, Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences. J. Biol. Chem. 275: 37137–37149.

    Article  CAS  PubMed  Google Scholar 

  • Grassme, H., Jendrossek, V., Riehle, A., von Kurthy, G., Berger, J., Schwarz, H., Weller, M., Kolesnick, R., and Gulbins, E., 2003, Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts. Nat. Med. 9: 322–330.

    Article  CAS  PubMed  Google Scholar 

  • Graziani, A., Rosker, C., Kohlwein, S.D., Zhu, M.X., Romanin, C., Sattler, W., Groschner, K., and Poteser, M., 2006, Cellular cholesterol controls TRPC3 function: evidence from a novel dominant-negative knockdown strategy. Biochem. J. 396: 147–55.

    Article  CAS  PubMed  Google Scholar 

  • Grimaldi, M., Favit, A., Alkon, D.L., 1999, cAMP-induced cytoskeleton rearrangement increases calcium transients through the enhancement of capacitative calcium entry. J. Biol. Chem. 274: 33557–64.

    Article  CAS  PubMed  Google Scholar 

  • Gutman, G.A., Chandy, K.G., Grissmer, S., Lazdunski, M., McKinnon, D., Pardo, L.A., Robertson, G.A., Rudy, B., Sanguinetti, M.C., Stuhmer, W., and Wang, X., 2005, International Union of Pharmacology. LIII. Nomenclature and Molecular Relationships of Voltage-Gated Potassium Channels. Pharmacol. Rev. 57: 473–508.

    Article  CAS  PubMed  Google Scholar 

  • Haass, F.A., Jonikas, M., Walter, P., Weissman, J.S., Jan, Y.-N., Jan, L.Y., and Schuldiner, M., 2007, Identification of yeast proteins necessary for cell-surface function of a potassium channel. Proc. Natl. Acad. Sci. U.S.A. 104: 18079–18084.

    Article  CAS  PubMed  Google Scholar 

  • Hajdú, P., Varga, Z., Pieri, C., Panyi, G., and Gáspár, R.J., 2003, Cholesterol modifies the gating of Kv1.3 in human T lymphocytes. Pflugers Arch. 445: 674–682.

    PubMed  Google Scholar 

  • Hamill, O.P., and Martinac, B., 2001, Molecular basis of mechanotransduction in living cells. Physiol. Rev. 81: 685–740.

    CAS  PubMed  Google Scholar 

  • Hamill, O.P., and McBride, J.D.W., 1996, The pharmacology of mechanogated membrane ion channels. Pharmacol. Rev. 48: 231–252.

    CAS  PubMed  Google Scholar 

  • Hanwell, D., Ishikawa, T., Saleki, R., and Rotin, D., 2002, Trafficking and Cell Surface Stability of the Epithelial Na+ Channel Expressed in Epithelial Madin-Darby Canine Kidney Cells. J. Biol. Chem. 277: 9772–9779.

    Article  CAS  PubMed  Google Scholar 

  • Hartwig, J.H., 1992, Mechanisms of actin rearrangements mediating platelet activation. J. Cell Biol. 118: 1421–42.

    Article  CAS  PubMed  Google Scholar 

  • Heaps, C.L., Tharp, D.L., and Bowles, D.K., 2005, Hypercholesterolemia abolishes voltage-dependent K+ channel contribution to adenosine-mediated relaxation in porcine coronary arterioles. Am. J. Physiol. Heart Circ. Physiol. 288: H568–576.

    Article  CAS  PubMed  Google Scholar 

  • Hibino, H., and Kurachi, Y., 2007, Distinct detergent-resistant membrane microdomains (lipid rafts) respectively harvest K+ and water transport systems in brain astroglia. Euro. J. Neurosci. 26: 2539–2555.

    Article  Google Scholar 

  • Hilgemann, D.W., Feng, S., and Nasuhoglu, C., 2001, The complex and intriguing lives of PIP2 with ion channels and transporters. Sci. STKE. 111: RE19.

    Google Scholar 

  • Hill, W.G., An, B., and Johnson, J.P., 2002, Endogenously expressed epithelial sodium channel is present in lipid rafts in A6 cells. J. Biol. Chem. 277: 33541–33544.

    Article  CAS  PubMed  Google Scholar 

  • Hill, W.G., Butterworth, M.B., Wang, H., Edinger, R.S., Lebowitz, J., Peters, K.W., Frizzell, R.A., and Johnson, J.P., 2007, The Epithelial Sodium Channel (ENaC) Traffics to Apical Membrane in Lipid Rafts in Mouse Cortical Collecting Duct Cells. J. Biol. Chem. 282: 37402–37411.

    Article  CAS  PubMed  Google Scholar 

  • Hinzpeter, A., Fritsch, J., Borot, F., Trudel, S., Vieu, D.L., Brouillard, F., Baudouin-Legros, M., Clain, J., Edelman, A., and Ollero, M., 2007, Membrane cholesterol content modulates ClC-2 gating and sensitivity to oxidative stress. J. Biol. Chem. 282: 2423–2432.

    Article  CAS  PubMed  Google Scholar 

  • Hoffmann, E.K., Lambert, I.H., and Pedersen, S.F., 2009, Physiology of cell volume regulation in vertebrates. Physiol. Rev. 89: 193–277.

    Article  CAS  PubMed  Google Scholar 

  • Huber, T.B., Schermer, B., Muller, R.U., Hohne, M., Bartram, M., Calixto, A., Hagmann, H., Reinhardt, C., Koos, F., Kunzelmann, K., Shirokova, E., Krautwurst, D., Harteneck, C., Simons, M., Pavenstädt, H., Kerjaschki, D., Thiele, C., Walz, G., Chalfie, M., and Benzing, T., 2006, Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels. Proc. Natl. Acad. Sci. U.S.A. 103: 17079–86.

    Article  CAS  PubMed  Google Scholar 

  • Ingueneau, C., Huynh-Do, U., Marcheix, B., Athias, A., Gambert. P., Nègre-Salvayre, A., Salvayre, R., and Vindis, C., 2008, TRPC1 is regulated by caveolin-1 and is involved in oxidized LDL-induced apoptosis of vascular smooth muscle cells. J. Cell Mol. Med. (Epub ahead of print).

    Google Scholar 

  • Jena, B.P., 2008, Porosome: the universal molecular machinery for cell secretion. Mol. Cells 26: 517–529.

    CAS  PubMed  Google Scholar 

  • Jennings, L.J., Xu, Q.-W., Firth, T.A., Nelson, M.T., and Mawe, G.M., 1999, Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle. Am. J. Physiol. 277: G1017–1026.

    CAS  PubMed  Google Scholar 

  • Jentsch, T.J., 2008, CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. Crit. Rev. Biochem. Mol. Biol. 43: 3–36.

    Article  CAS  PubMed  Google Scholar 

  • Jentsch, T.J., Stein, V., Weinreich, F., and Zdebik, A.A., 2002, Molecular Structure and Physiological Function of Chloride Channels. Physiol. Rev. 82: 503–568.

    CAS  PubMed  Google Scholar 

  • Jeremy, R.W., and McCarron, H., 2000, Effect of hypercholesterolemia on Ca2+-dependent K+ channel-mediated vasodilatation in vivo. Am. J. Physiol. 279: H1600–1608.

    CAS  Google Scholar 

  • Jiang, C., Fang, S.L., Xiao, Y.F., O’Connor, S.P., Nadler, S.G., Lee, D.W., Jefferson, D.M., Kaplan, J.M., Smith, A.E., and Cheng, S.H., 1998, Partial restoration of cAMP-stimulated CFTR chloride channel activity in DeltaF508 cells by deoxyspergualin. Am. J. Physiol. 275: C171–178.

    CAS  PubMed  Google Scholar 

  • Jiang, J., Thorén, P., Caligiuri, G., Hansson, G.K., and Pernow, J., 1999, Enhanced phenylephrine-induced rhythmic activity in the atherosclerotic mouse aorta via an increase in opening of KCa channels: relation to Kv channels and nitric oxide. Br. J. Pharmacol. 128: 637–646.

    Article  CAS  PubMed  Google Scholar 

  • Kannan, K.B., Barlos, D., and Hauser, C.J., 2007, Free cholesterol alters lipid raft structure and function regulating neutrophil Ca2+ entry and respiratory burst: correlations with calcium channel raft trafficking. J. Immunol. 178: 5253–61.

    CAS  PubMed  Google Scholar 

  • Khan, R.N., Matharoo-Ball, B., Arulkumaran, S., and Ashford, M.L., 2001, Potassium channels in the human myometrium. Exp. Physiol. 86: 255–264.

    Article  CAS  PubMed  Google Scholar 

  • Kindzelskii, A.L., Sitrin, R.G., and Petty, H.R., 2004, Cutting edge: optical microspectrophotometry supports the existence of gel phase lipid rafts at the lamellipodium of neutrophils: apparent role in calcium signalling. J. Immunol. 172: 4681–5.

    CAS  PubMed  Google Scholar 

  • King, J.T., Lovell, P.V., Rishniw, M., Kotlikoff, M.I., Zeeman, M.L., and McCobb, D.P., 2006, Beta2 and beta4 subunits of BK channels confer differential sensitivity to acute modulation by steroid hormones. J. Neurophysiol. 95: 2878–2888.

    Article  CAS  PubMed  Google Scholar 

  • Klausen, T.K., Hougaard, C., Hoffmann, E.K., and Pedersen, S.F., 2006, Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin. Am. J. Physiol. Cell. Physiol. 291: C757–771.

    Article  CAS  PubMed  Google Scholar 

  • Kopito, R.R., 1999, Biosynthesis and degradation of CFTR. Physiol. Rev. 79: S167–173.

    CAS  PubMed  Google Scholar 

  • Kowalski, M.P., and Pier, G.B., 2004, Localization of Cystic Fibrosis Transmembrane Conductance Regulator to Lipid Rafts of Epithelial Cells Is Required for Pseudomonas aeruginosa-Induced Cellular Activation. J. Immunol. 172: 418–425.

    CAS  PubMed  Google Scholar 

  • Kubo, Y., Adelman, J.P., Clapham, D.E., Jan, L.Y., Karschin, A., Kurachi, Y., Lazdunski, M., Nichols, C.G., Seino, S., and Vandenberg, C.A., 2005, International Union of Pharmacology. LIV. Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels. Pharmacol. Rev. 57: 509–526.

    Article  CAS  PubMed  Google Scholar 

  • Kwiatek, A.M., Minshall, R.D., Cool, D.R., Skidgel, R.A., Malik, A.B., and Tiruppathi, C., 2006, Caveolin-1 regulates store-operated Ca2+ influx by binding of its scaffolding domain to transient receptor potential channel-1 in endothelial cells. Mol. Pharmacol. 70: 1174–83.

    Article  CAS  PubMed  Google Scholar 

  • Lam, R.S., Shaw, A.R., and Duszyk, M., 2004, Membrane cholesterol content modulates activation of BK channels in colonic epithelia. Biochim. Biophys. Acta 1667: 241–248.

    Article  CAS  PubMed  Google Scholar 

  • Lambert, I.H., 2004, Regulation of the cellular content of the organic osmolyte taurine in mammalian cells. Neurochem. Res. 29: 27–63.

    Article  CAS  PubMed  Google Scholar 

  • Langeslag, M., Clark, K., Moolenaar, W.H., van Leeuwen, F.N., and Jalink, K., 2007, Activation of TRPM7 channels by phospholipase C-coupled receptor agonists. J. Biol. Chem. 282: 232–9.

    Article  CAS  PubMed  Google Scholar 

  • Langhorst, M.F., Reuter, A., and Stuermer, C.A., 2005, Scaffolding microdomains and beyond: the function of reggie/flotillin proteins. Cell Mol. Life Sci. 62: 2228–2240.

    Article  CAS  PubMed  Google Scholar 

  • Ledoux, J., Werner, M.E., Brayden, J.E., and Nelson, M.T., 2006, Calcium-activated potassium channels and the regulation of vascular tone. Physiol. (Bethesda) 21: 69–78.

    CAS  Google Scholar 

  • Lee, I.-H., Campbell, C.R., Song, S.-H., Day, M.L., Kumar, S., Cook, D.I., and Dinudom, A., 2009, The Activity of the Epithelial Sodium Channels Is Regulated by Caveolin-1 via a Nedd4-2-dependent Mechanism. J. Biol. Chem. 284: 12663–12669.

    Article  CAS  PubMed  Google Scholar 

  • Lee, T.-M., Lin, M.-S., Chou, T.-F., Tsai, C.-H., and Chang, N.-C., 2004, Effect of pravastatin on left ventricular mass by activation of myocardial KATP channels in hypercholesterolemic rabbits. Atherosclerosis 176: 273.

    Article  CAS  PubMed  Google Scholar 

  • Levitan, I., Christian, A.E., Tulenko, T.N., and Rothblat, G.H., 2000, Membrane cholesterol content modulates activation of volume-regulated anion current (VRAC) in bovine endothelial cells. J. Gen. Physiol. 115: 405–416.

    Article  CAS  PubMed  Google Scholar 

  • Levitan, I., and Gooch, K.J., 2007, Lipid Rafts in Membrane-Cytoskeleton Interactions and Control of Cellular Biomechanics: Actions of oxLDL. Antioxidants & Redox Signalling 9: 1519–1534.

    Article  CAS  Google Scholar 

  • Lewis, R.S., 2007, The molecular choreography of a store-operated calcium channel. Nature 446: 284–7.

    Article  CAS  PubMed  Google Scholar 

  • Lim, C.H., Bijvelds, M.J., Nigg, A., Schoonderwoerd, K., Houtsmuller, A.B., de Jonge, H.R., and Tilly, B.C., 2007, Cholesterol depletion and genistein as tools to promote F508delCFTR retention at the plasma membrane. Cell Physiol. Biochem. 20: 473–482.

    Article  CAS  PubMed  Google Scholar 

  • Lim, C.H., Schoonderwoerd, K., Kleijer, W.J., de Jonge, H.R., and Tilly, B.C., 2006, Regulation of the cell swelling-activated chloride conductance by cholesterol-rich membrane domains. Acta Physiol. 187: 295–303.

    Article  CAS  Google Scholar 

  • Lin, M.W., Wu, A.Z., Ting, W.H., Li, C.L., Cheng, K.S., and Wu, S.N., 2006, Changes in membrane cholesterol of pituitary tumor (GH3) cells regulate the activity of large-conductance Ca2+-activated K+ channels. Chin. J. Physiol. 49: 1–13.

    CAS  PubMed  Google Scholar 

  • Liou, J., Kim, M.L., Heo, W.D., Jones, J.T., Myers, J.W., Ferrell, J.E., Jr., and Meyer, T., 2005, STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol 15: 1235–41.

    Article  CAS  PubMed  Google Scholar 

  • Liu, M., Huang, W., Wu, D., Priestley, J.V., 2006, TRPV1, but not P2X, requires cholesterol for its function and membrane expression in rat nociceptors. Eur. J. Neurosci. 24: 1–6.

    Article  CAS  PubMed  Google Scholar 

  • Lockwich, T., Singh, B.B., Liu, X., and Ambudkar, I.S., 2001, Stabilization of cortical actin induces internalization of transient receptor potential 3 (Trp3)-associated caveolar Ca2+ signalling complex and loss of Ca2+ influx without disruption of Trp3-inositol trisphosphate receptor association. J. Biol. Chem. 276: 42401–8.

    Article  CAS  PubMed  Google Scholar 

  • Lockwich, T.P., Liu, X., Singh, B.B., Jadlowiec, J., Weiland, S., and Ambudkar, I.S., 2000, Assembly of Trp1 in a signalling complex associated with caveolin-scaffolding lipid raft domains. J. Biol. Chem. 275: 11934–42.

    Article  CAS  PubMed  Google Scholar 

  • Logothetis, D.E., Jin, T., Lupyan, D., and Rosenhouse-Dantsker, A., 2007, Phosphoinositide-mediated gating of inwardly rectifying K+ channels. Pflugers Arch. 455: 83–95.

    Article  CAS  PubMed  Google Scholar 

  • Logsdon, N.J., Kang, J., Togo, J.A., Christian, E.P., and Aiyar, J., 1997, A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes. J. Biol. Chem. 272: 32723–32726.

    Article  CAS  PubMed  Google Scholar 

  • Lucken-Ardjomande, S., Montessuit, S., and Martinou, J.C., 2008, Bax activation and stress-induced apoptosis delayed by the accumulation of cholesterol in mitochondrial membranes. Cell Death Differ. 15: 484–493.

    Article  CAS  PubMed  Google Scholar 

  • Lundbaek, J.A., and Andersen, O.S., 1999, Spring constants for channel-induced lipid bilayer deformations estimates using gramicidin channels. Biophys. J. 76: 889–895.

    Article  CAS  PubMed  Google Scholar 

  • Lundbaek, J.A., Birn, P., Hansen, A.J., and Andersen, O.S., 1996, Membrane stiffness and channel function. Biochemistry 35: 3825–3830.

    Article  CAS  PubMed  Google Scholar 

  • Lundbaek, J.A., Birn, P., Hansen, A.J., Sogaard, R., Nielsen, C., Girshman, J., Bruno, M.J., Tape, S.E., Egebjerg, J., Greathouse, D.V., Mattice, G.L., Koeppe, R.E., II, and Andersen, O.S., 2004, Regulation of Sodium Channel Function by Bilayer Elasticity: The Importance of Hydrophobic Coupling. Effects of Micelle-forming Amphiphiles and Cholesterol. J. Gen. Physiol. 123: 599–621.

    Article  CAS  PubMed  Google Scholar 

  • Maguy, A., Hebert, T.E., and Nattel, S., 2006, Involvement of lipid rafts and caveolae in cardiac ion channel function. Cardiovasc. Res. 69: 798.

    Article  CAS  PubMed  Google Scholar 

  • Marsh, D., and Barrantes, F.J., 1978, Immobilized lipid in acetylcholine receptor-rich membranes from Torpedo marmorata. Proc. Natl. Acad. Sci. U.S.A. 75: 4329–4333.

    Article  CAS  PubMed  Google Scholar 

  • Martens, J.R., Navarro-Polanco, R., Coppock, E.A., Nishiyama, A., Parshley, L., Grobaski, T.D., and Tamkun, M.M., 2000, Differential Targeting of Shaker-like Potassium Channels to Lipid Rafts. J. Biol. Chem. 275: 7443–7446.

    Article  CAS  PubMed  Google Scholar 

  • Martens, J.R., O’Connell, K., and Tamkun, M., 2004, Targeting of ion channels to membrane microdomains: localization of KV channels to lipid rafts. Trends Pharmacol. Sci. 25: 16–21.

    Article  CAS  PubMed  Google Scholar 

  • Martens, J.R., Sakamoto, N., Sullivan, S.A., Grobaski, T.D., and Tamkun, M.M., 2001, Isoform-specific Localization of Voltage-gated K+ Channels to Distinct Lipid Raft Populations. Targeting of Kv1.5 to caveolae. J. Biol. Chem. 276: 8409–8414.

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Abundis, E., Garcia, N., Correa, F., Franco, M., and Zazueta, C., 2007, Changes in specific lipids regulate BAX-induced mitochondrial permeability transition. FEBS J. 274: 6500–6510.

    CAS  PubMed  Google Scholar 

  • Mathew, V., and Lerman, A., 2001, Altered effects of potassium channel modulation in the coronary circulation in experimental hypercholesterolemia. Atherosclerosis 154: 329–335.

    Article  CAS  PubMed  Google Scholar 

  • McEwen, D.P., Li, Q., Jackson, S., Jenkins, P.M., and Martens, J.R., 2008, Caveolin Regulates Kv1.5 Trafficking to Cholesterol-Rich Membrane Microdomains. Mol. Pharmacol. 73: 678–685.

    Article  CAS  PubMed  Google Scholar 

  • Mohler Iii, E.R., Fang, Y., Gusic Shaffer, R., Moore, J., Wilensky, R.L., Parmacek, M., and Levitan, I., 2007, Hypercholesterolemia suppresses Kir channels in porcine bone marrow progenitor cells in vivo. Biochem. Biophys. Res. Comm. 358: 317–324.

    Article  CAS  Google Scholar 

  • Morachevskaya, E., Sudarikova, A., and Negulyaev, Y., 2007, Mechanosensitive channel activity and F-actin organization in cholesterol-depleted human leukaemia cells. Cell Biol. Int. 31: 374–381.

    Article  CAS  PubMed  Google Scholar 

  • Morenilla-Palao, C., Pertusa, M., Meseguer, V., Cabedo, H., and Viana, F., 2009, Lipid raft segregation modulates TRPM8 channel activity. J. Biol. Chem. 284: 9215–24.

    Article  CAS  PubMed  Google Scholar 

  • Murata, T., Lin, M.I., Stan, R.V., Bauer, P.M., Yu, J., and Sessa, W.C., 2007, Genetic evidence supporting caveolae microdomain regulation of calcium entry in endothelial cells. J. Biol. Chem. 282: 16631–43.

    Article  CAS  PubMed  Google Scholar 

  • Najibi, S., and Cohen, R.A., 1995, Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO. Am. J. Physiol. Heart Circ. Physiol. 269: H805–811.

    CAS  Google Scholar 

  • Najibi, S., Cowan, C.L., Palacino, J.J., and Cohen, R.A., 1994, Enhanced role of potassium channels in relaxations to acetylcholine in hypercholesterolemic rabbit carotid artery. Am J. Physiol. Heart Circ. Physiol. 266: H2061–2067.

    CAS  Google Scholar 

  • Nam, J.H., Lee, H.-S., Nguyen, Y.H., Kang, T.M., Lee, S.W., Kim, H.-Y., Kim, S.J., Earm, Y.E., and Kim, S.J., 2007, Mechanosensitive activation of K+ channel via phospholipase C-induced depletion of phosphatidylinositol 4,5-bisphosphate in B lymphocytes. J. Physiol. 582: 977.

    Article  CAS  PubMed  Google Scholar 

  • Nichols, C., and Lopatin, A., 1997, Inward rectifier potassium channels. Annu. Rev. Physiol. 59.

    Google Scholar 

  • Nichols, C.G., 2006, KATP channels as molecular sensors of cellular metabolism. Nature 440: 470.

    Article  CAS  PubMed  Google Scholar 

  • Nilius, B., and Droogmans, G., 2001, Ion channels and their functional role in vascular endothelium. Physiol. Rev. 81: 1415–1459.

    CAS  PubMed  Google Scholar 

  • Nilius, B., and Droogmans, G., 2003, Amazing chloride channels: an overview. Acta Physiol. Scand. 177: 119–147.

    Article  CAS  PubMed  Google Scholar 

  • O’Connell, K.M.S., Martens, J.R., and Tamkun, M.M., 2004, Localization of Ion Channels to Lipid Raft Domains within the Cardiovascular System. Trends Cardiovasc. Med. 14: 37.

    Article  PubMed  CAS  Google Scholar 

  • O’Connell, K.M.S., and Tamkun, M.M., 2005, Targeting of voltage-gated potassium channel isoforms to distinct cell surface microdomains. J. Cell Sci. 118: 2155–2166.

    Article  PubMed  CAS  Google Scholar 

  • O’Connell, K.M.S., Whitesell, J.D., and Tamkun, M.M., 2008, Localization and mobility of the delayed-rectifer K+ channel Kv2.1 in adult cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 294: H229–237.

    Article  PubMed  CAS  Google Scholar 

  • Olesen, S.-P., Clapham, D.E., and Davies, P.F., 1988, Hemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331: 168–170.

    Article  CAS  PubMed  Google Scholar 

  • Ortenblad, N., Young, J.F., Oksbjerg, N., Nielsen, J.H., and Lambert, I.H., 2003, Reactive oxygen species are important mediators of taurine release from skeletal muscle cells. Am J. Physiol. Cell Physiol. 284: C1362–1373.

    CAS  PubMed  Google Scholar 

  • Palygin, O.A., Pettus, J.M., and Shibata, E.F., 2008, Regulation of caveolar cardiac sodium current by a single Gs{alpha} histidine residue. Am. J. Physiol. Heart Circ. Physiol. 294: H1693–1699.

    Article  CAS  PubMed  Google Scholar 

  • Pani B, Ong HL, Liu X, Rauser K, Ambudkar IS, Singh BB., 2008, Lipid rafts determine clustering of STIM1 in endoplasmic reticulum-plasma membrane junctions and regulation of store-operated Ca2+ entry (SOCE). J. Biol. Chem. 283: 17333–40.

    Article  CAS  PubMed  Google Scholar 

  • Panyi, G., Bagdany, M., Bodnar, A., Vamosi, G., Szentesi, G., Jenei, A., Matyus, L., Varga, S., Waldmann, T.A., Gaspar, R., and Damjanovich, S., 2003, Colocalization and nonrandom distribution of Kv1.3 potassium channels and CD3 molecules in the plasma membrane of human T lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 100: 2592–2597.

    Article  CAS  PubMed  Google Scholar 

  • Panyi, G., Vamosi, G., Bacso, Z., Bagdany, M., Bodnar, A., Varga, Z., Gaspar, R., Matyus, L., and Damjanovich, S., 2004, Kv1.3 potassium channels are localized in the immunological synapse formed between cytotoxic and target cells. Proc. Natl. Acad. Sci. U.S.A. 101: 1285–1290.

    Article  CAS  PubMed  Google Scholar 

  • Pedersen, S.F., Owsianik, G., and Nilius, B., 2005, TRP channels: an overview. Cell Calcium 38: 233–52.

    Article  CAS  PubMed  Google Scholar 

  • Perry, M.D., and Sandle, G.I., 2009, Regulation of colonic apical potassium (BK) channels by cAMP and somatostatin. Am. J. Physiol. Gastrointest. Liver Physiol. 297: G159–167.

    Article  CAS  PubMed  Google Scholar 

  • Pike, L., and Casey, L., 1996, Localization and turnover of phosphatidylinositol 4,5-bisphospate in caveolin-enriched membrane domains. J. Biol. Chem. 271: 26453–26456.

    Article  CAS  PubMed  Google Scholar 

  • Pike, L.J., 2006, Rafts defined: a report on the Keystone symposium on lipid rafts and cell function. J. Lipid Res. 47: 1597–1598.

    Article  CAS  PubMed  Google Scholar 

  • Pongo, E., Balla, Z., Mubagwa, K., Flameng, W., Edes, I., Szilvassy, Z., and Ferdinandy, P., 2001, Deterioration of the protein kinase C-KATP channel pathway in regulation of coronary flow in hypercholesterolaemic rabbits. Euro. J. Pharmacol. 418: 217.

    Article  CAS  Google Scholar 

  • Popp B, Schmid A, and Benz R., 1995, Role of sterols in the functional reconstitution of water-soluble mitochondrial porins from different organisms. Biochemistry. 34: 3352–3361.

    Google Scholar 

  • Pouvreau, S., Berthier, C., Blaineau, S., Amsellem, J., Coronado, R., and Strube, C., 2004, Membrane cholesterol modulates dihydropyridine receptor function in mice fetal skeletal muscle cells. J. Physiol. (Lond.) 555: 365–381.

    Article  CAS  Google Scholar 

  • Prince, L.S., and Welsh, M.J., 1999, Effect of subunit composition and Liddle’s syndrome mutations on biosynthesis of ENaC. Am. J. Physiol. Cell Physiol. 276: C1346–1351.

    CAS  Google Scholar 

  • Rehberg, B., Urban, B.W., and Duch, D.S., 1995, The membrane lipid cholesterol modulates anesthetic actions on a human brain ion channel. Anesthesiology 82: 749–758.

    Article  CAS  PubMed  Google Scholar 

  • Remillard, C.V., and Yuan, J.X., 2006, Transient receptor potential channels and caveolin-1: good friends in tight spaces. Mol. Pharmacol. 70: 1151–4.

    Article  CAS  PubMed  Google Scholar 

  • Ren, Y.J., Xu, X.H., Zhong, C.B., Feng, N., and Wang, X.L., 2001, Hypercholesterolemia alters vascular functions and gene expression of potassium channels in rat aortic smooth muscle cells. Acta Pharmacol. Sin. 22: 274–278.

    CAS  PubMed  Google Scholar 

  • Romanenko, V.G., Fang, Y., Byfield, F., Travis, A.J., Vandenberg, C.A., Rothblat, G.H., and Levitan, I., 2004a, Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels. Biophys. J. 87: 3850–3861.

    Article  CAS  PubMed  Google Scholar 

  • Romanenko, V.G., Nakamoto, T., Srivastava, A., Begenisich, T., and Melvin, J.E., 2007, Regulation of membrane potential and fluid secretion by Ca2+-activated K+ channels in mouse submandibular glands. J. Physiol. 581: 801–817.

    Article  PubMed  CAS  Google Scholar 

  • Romanenko, V.G., Roser, K.S., Melvin, J.E., and Begenisich, T., 2009, The role of cell cholesterol and the cytoskeleton in the interaction between IK1 and maxi-K channels. Am J. Physiol. Cell Physiol. 296: C878–888.

    Article  CAS  PubMed  Google Scholar 

  • Romanenko, V.G., Rothblat, G.H., and Levitan, I., 2002, Modulation of endothelial inward rectifier K+ current by optical isomers of cholesterol. Biophys. J. 83: 3211–3222.

    Article  CAS  PubMed  Google Scholar 

  • Romanenko, V.G., Rothblat, G.H., and Levitan, I., 2004b, Sensitivity of volume-regulated anion current to cholesterol structural analogues. J. Gen. Physiol. 123: 77–88.

    Article  CAS  PubMed  Google Scholar 

  • Roos, J., DiGregorio, P.J., Yeromin, A.V., Ohlsen, K., Lioudyno, M., Zhang, S., Safrina, O., Kozak, J.A., Wagner, S.L., Cahalan, M.D., Veliçelebi, G., and Stauderman, K.A., 2005, STIM1, an essential and conserved component of store-operated Ca2+ channel function. J. Cell. Biol. 169: 435–45.

    Article  CAS  PubMed  Google Scholar 

  • Rostovtseva, T.K., Antonsson, B., Suzuki, M., Youle, R.J., Colombini, M., and Bezrukov, S.M., 2004, Bid, but not Bax, regulates VDAC channels. J. Biol. Chem. 279: 13575–13583.

    Article  CAS  PubMed  Google Scholar 

  • Rostovtseva, T.K., and Bezrukov, S.M., 2008, VDAC regulation: role of cytosolic proteins and mitochondrial lipids. J. Bioenerg. Biomembr. 40: 163–170.

    Article  CAS  PubMed  Google Scholar 

  • Rowntree, R.K., and Harris, A., 2003, The phenotypic consequences of CFTR mutations. Ann. Hum. Genet. 67: 471–485.

    Article  CAS  PubMed  Google Scholar 

  • Sachs, F., and Morris, C., 1998, Mechanosensitive ion channels in nonspecialized cells. Rev. Physiol. Biochem. Pharmacol. 132: 1–78.

    Article  CAS  PubMed  Google Scholar 

  • Sah, P., and Faber, E.S., 2002, Channels underlying neuronal calcium-activated potassium currents. Prog. Neurobiol. 66: 345–353.

    Article  CAS  PubMed  Google Scholar 

  • Salkoff, L., Butler, A., Ferreira, G., Santi, C., and Wei, A., 2006, High-conductance potassium channels of the SLO family. Nat. Rev. Neurosci. 7: 921–931.

    Article  CAS  PubMed  Google Scholar 

  • Sampson, L.J., Davies, L.M., Barrett-Jolley, R., Standen, N.B., and Dart, C., 2007, Angiotensin II-activated protein kinase C targets caveolae to inhibit aortic ATP-sensitive potassium channels. Cardiovasc. Res. 76: 61–70.

    Article  CAS  PubMed  Google Scholar 

  • Sampson, L.J., Hayabuchi, Y., Standen, N.B., and Dart, C., 2004, Caveolae localize protein kinase A signalling to arterial ATP-sensitive potassium channels. Circ. Res. 95: 1012–1018.

    Article  CAS  PubMed  Google Scholar 

  • Santi, C.M.D., Butler, A., Kuhn, J., Wei, A.D., and Salkoff, L.D., 2009, Bovine and mouse SLO3 K+ channels:evolutionary divergence points to a RCK1 region of critical function. J. Biol. Chem. 284: 21589–98.

    Article  CAS  PubMed  Google Scholar 

  • Schreiber, M., Wei, A., Yuan, A., Gaut, J., Saito, M., and Salkoff, L., 1998, Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes. J. Biol. Chem. 273: 3509–3516.

    Article  CAS  PubMed  Google Scholar 

  • Schwiebert, E.M., Egan, M.E., Hwang, T.H., Fulmer, S.B., Allen, S.S., Cutting, G.R., and Guggino, W.B., 1995, CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell 81: 1063–1073.

    Article  CAS  PubMed  Google Scholar 

  • Shennan, D.B., 2008, Swelling-induced taurine transport: relationship with chloride channels, anion-exchangers and other swelling-activated transport pathways. Cell Physiol. Biochem. 21: 15–28.

    Article  CAS  PubMed  Google Scholar 

  • Shlyonsky, V.G., Mies, F., and Sariban-Sohraby, S., 2003, Epithelial sodium channel activity in detergent-resistant membrane microdomains. Am. J. Physiol. Renal Physiol. 284: F182–188.

    CAS  PubMed  Google Scholar 

  • Shmygol, A., Noble, K., and Wray, S., 2007, Depletion of membrane cholesterol eliminates the Ca2+-activated component of outward potassium current and decreases membrane capacitance in rat uterine myocytes. J. Physiol. 581: 445–456.

    Article  CAS  PubMed  Google Scholar 

  • Shoshan-Barmatz, V., Israelson, A., Brdiczka, D., and Sheu, S.S., 2006, The voltage-dependent anion channel (VDAC): function in intracellular signalling, cell life and cell death. Curr. Pharm. Des. 12: 2249–2270.

    Article  CAS  PubMed  Google Scholar 

  • Singh, A.K., Schultz, B.D., Katzenellenbogen, J.A., Price, E.M., Bridges, R.J., and Bradbury, N.A., 2000, Estrogen inhibition of cystic fibrosis transmembrane conductance regulator-mediated chloride secretion. J. Pharmacol. Exp. Ther. 295: 195–204.

    CAS  PubMed  Google Scholar 

  • Sobey, C.G., 2001, Potassium Channel Function in Vascular Disease. Arterioscler Thromb. Vasc. Biol. 21: 28–38.

    CAS  PubMed  Google Scholar 

  • Sprossmann, F., Pankert, P., Sausbier, U., Wirth, A., Zhou, X.B., Madlung, J., Zhao, H., Bucurenciu, I., Jakob, A., Lamkemeyer, T., Neuhuber, W., Offermanns, S., Shipston, M.J., Korth, M., Nordheim, A., Ruth, P., and Sausbier, M., 2009, Inducible knockout mutagenesis reveals compensatory mechanisms elicited by constitutive BK channel deficiency in overactive murine bladder. FEBS J. 276: 1680–1697.

    Article  CAS  PubMed  Google Scholar 

  • Stutzin, A., and Hoffmann, E.K., 2006, Swelling-activated ion channels: functional regulation in cell-swelling, proliferation and apoptosis. Acta Physiol. (Oxf) 187: 27–42.

    Article  CAS  Google Scholar 

  • Suzuki, M., Morita, T., and Iwamoto, T., 2006, Diversity of Cl- channels. Cell Mol. Life Sci. 63: 12–24.

    Article  CAS  PubMed  Google Scholar 

  • Taverna, E., Saba, E., Rowe, J., Francolini, M., Clementi, F., and Rosa, P., 2004, Role of Lipid Microdomains in P/Q-type Calcium Channel (Cav2.1) Clustering and Function in Presynaptic Membranes. J. Biol. Chem. 279: 5127–5134.

    Article  CAS  PubMed  Google Scholar 

  • Thiemann, A., Grunder, S., Pusch, M., and Jentsch, T.J., 1992, A chloride channel widely expressed in epithelial and non-epithelial cells. Nature 356: 57–60.

    Article  CAS  PubMed  Google Scholar 

  • Tikku, S., Epshtein, Y., Collins, H., Travis, A.J., Rothblat, G.H., and Levitan, I., 2007, Relationship between Kir2.1/Kir2.3 activity and their distribution between cholesterol-rich and cholesterol-poor membrane domains. Am. J. Physiol. Cell Physiol. 293: C440–450.

    Article  CAS  PubMed  Google Scholar 

  • Torihashi, S., Fujimoto, T., Trost, C., and Nakayama, S., 2002, Calcium oscillation linked to pacemaking of interstitial cells of Cajal: requirement of calcium influx and localization of TRP4 in caveolae. J. Biol. Chem. 277: 19191–7.

    Article  CAS  PubMed  Google Scholar 

  • Toselli, M., Biella, G., Taglietti, V., Cazzaniga, E., and Parenti, M., 2005, Caveolin-1 Expression and Membrane Cholesterol Content Modulate N-Type Calcium Channel Activity in NG108-15 Cells. Biophys. J. 89: 2443–2457.

    Article  CAS  PubMed  Google Scholar 

  • Toyama, K., Wulff, H., Chandy, K.G., Azam, P., Raman, G., Saito, T., Fujiwara, Y., Mattson, D.L., Das, S., Melvin, J.E., Pratt, P.F., Hatoum, O.A., Gutterman, D.D., Harder, D.R., and Miura, H., 2008, The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans. J. Clin. Invest. 118: 3025.

    Article  CAS  PubMed  Google Scholar 

  • Trouet, D., Hermans, D., Droogmans, G., Nilius, B., and Eggermont, J., 2001, Inhibition of Volume-Regulated Anion Channels by Dominant-Negative Caveolin-1. Biochem. Biophys. Res. Comm. 284: 461.

    Article  CAS  PubMed  Google Scholar 

  • Trouet, D., Nilius, B., Jacobs, A., Remacle, C., Droogmans, G., and Eggermont, J., 1999, Caveolin-1 modulates the activity of the volume-regulated chloride channel. J. Physiol. 520 Pt 1: 113–119.

    Article  CAS  PubMed  Google Scholar 

  • Tsujikawa, H., Song, Y., Watanabe, M., Masumiya, H., Gupte, S.A., Ochi, R., and Okada, T., 2008, Cholesterol depletion modulates basal L-type Ca2+ current and abolishes its -adrenergic enhancement in ventricular myocytes. Am. J. Physiol. Heart Circ. Physiol. 294: H285–292.

    Article  CAS  PubMed  Google Scholar 

  • Ullrich, N., Caplanusi, A., Brone, B., Hermans, D., Lariviere, E., Nilius, B., Van Driessche, W., and Eggermont, J., 2006, Stimulation by caveolin-1 of the hypotonicity-induced release of taurine and ATP at basolateral, but not apical, membrane of Caco-2 cells. Am. J. Physiol. Cell Physiol. 290: C1287–1296.

    Article  CAS  PubMed  Google Scholar 

  • Vandorpe, D.H., Shmukler, B.E., Jiang, L., Lim, B., Maylie, J., Adelman, J.P., de Franceschi, L., Cappellini, M.D., Brugnara, C., and Alper, S.L., 1998, cDNA cloning and functional characterization of the mouse Ca2+-gated K+ channel, mIK1. Roles in regulatory volume decrease and erythroid differentiation. J. Biol. Chem 273: 21542–21553.

    Article  CAS  PubMed  Google Scholar 

  • Vicente, R., Villalonga, N., Calvo, M., Escalada, A., Solsona, C., Soler, C., Tamkun, M.M., and Felipe, A., 2008, Kv1.5 Association Modifies Kv1.3 Traffic and Membrane Localization. J. Biol. Chem. 283: 8756–8764.

    Article  CAS  PubMed  Google Scholar 

  • Vij, N., Mazur, S., and Zeitlin, P.L., 2009, CFTR is a negative regulator of NFkappaB mediated innate immune response. PLoS ONE 4: e4664.

    Article  PubMed  CAS  Google Scholar 

  • Wang, D., Wang, W., Duan, Y., Sun, Y., Wang, Y., and Huang, P., 2008, Functional coupling of Gs and CFTR is independent of their association with lipid rafts in epithelial cells. Pflugers Arch. 456: 929–938.

    Article  CAS  PubMed  Google Scholar 

  • Wang, X.L., Ye, D., Peterson, T.E., Cao, S., Shah, V.H., Katusic, Z.S., Sieck, G.C., and Lee, H.C., 2005, Caveolae targeting and regulation of large conductance Ca2+-activated K+ channels in vascular endothelial cells. J. Biol. Chem. 280: 11656–11664.

    Article  CAS  PubMed  Google Scholar 

  • Weaver, A.K., Olsen, M.L., McFerrin, M.B., and Sontheimer, H., 2007, BK channels are linked to inositol 1,4,5-triphosphate receptors via lipid rafts: a novel mechanism for coupling [Ca2+](i) to ion channel activation. J. Biol. Chem. 282: 31558–31568.

    Article  CAS  PubMed  Google Scholar 

  • Wei, S.-P., Li, X.-Q., Chou, C.-F., Liang, Y.-Y., Peng, J.-B., Warnock, D., and Ma, H.-P., 2007, Membrane Tension Modulates the Effects of Apical Cholesterol on the Renal Epithelial Sodium Channel. J. Membrane Biol. 220: 21.

    Article  CAS  Google Scholar 

  • West, A., and Blazer-Yost, B., 2005, Modulation of basal and peptide hormone-stimulated Na transport by membrane cholesterol content in the A6 epithelial cell line. Cell Physiol. Biochem. 16: 263–270.

    Article  CAS  PubMed  Google Scholar 

  • Wiecha, J., Schläger, B., Voisard, R., Hannekum, A., Mattfeldt, T., and Hombach, V., 1997, Ca2+-activated K+ channels in human smooth muscle cells of coronary atherosclerotic plaques and coronary media segments. Basic Res. Cardiol. 92: 233–239.

    Article  CAS  PubMed  Google Scholar 

  • Wong, W., and Schlichter, L.C., 2004, Differential Recruitment of Kv1.4 and Kv4.2 to Lipid Rafts by PSD-95. J. Biol. Chem. 279: 444–452.

    Article  CAS  PubMed  Google Scholar 

  • Wu, C.C., Su, M.J., Chi, J.F., Chen, W.J., Hsu, H.C., and Lee, Y.T., 1995, The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte. J Mol. Cell Cardiol. 27: 1263–1269.

    Article  CAS  PubMed  Google Scholar 

  • Xia, F., Gao, X., Kwan, E., Lam, P.P.L., Chan, L., Sy, K., Sheu, L., Wheeler, M.B., Gaisano, H.Y., and Tsushima, R.G., 2004, Disruption of Pancreatic {beta}-Cell Lipid Rafts Modifies Kv2.1 Channel Gating and Insulin Exocytosis. J. Biol. Chem. 279: 24685–24691.

    Article  CAS  PubMed  Google Scholar 

  • Xia, F., Leung, Y.M., Gaisano, G., Gao, X., Chen, Y., Manning Fox, J.E., Bhattacharjee, A., Wheeler, M.B., Gaisano, H.Y., and Tsushima, R.G., 2007, Targeting of Voltage-Gated K+ and Ca2+ Channels and Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptor Proteins to Cholesterol-Rich Lipid Rafts in Pancreatic {alpha}-Cells: Effects on Glucagon Stimulus-Secretion Coupling. Endocrinology 148: 2157–2167.

    Article  CAS  PubMed  Google Scholar 

  • Xu, X., and London, E., 2000, The effect of sterol structure on membrane lipid domains reveals how cholesterol can induce lipid domain formation. Biochemistry 39: 843–849.

    Article  CAS  PubMed  Google Scholar 

  • Yarbrough, T.L., Lu, T., Lee, H.-C., and Shibata, E.F., 2002, Localization of Cardiac Sodium Channels in Caveolin-Rich Membrane Domains: Regulation of Sodium Current Amplitude. Circ. Res. 90: 443–449.

    Article  CAS  PubMed  Google Scholar 

  • Yogi, A., Callera, G.E., Tostes, R., and Touyz, R.M., 2009, Bradykinin regulates calpain and proinflammatory signalling through TRPM7-sensitive pathways in vascular smooth muscle cells. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296: R201–7.

    CAS  PubMed  Google Scholar 

  • Yoo, D., Flagg, T.P., Olsen, O., Raghuram, V., Foskett, J.K., and Welling, P.A., 2004, Assembly and trafficking of a multiprotein ROMK (Kir 1.1) channel complex by PDZ interactions. J. Biol. Chem. 279: 6863–6873.

    Article  CAS  PubMed  Google Scholar 

  • Yuan, C., O’Connell, R.J., Feinberg-Zadek, P.L., Johnston, L.J., and Treistman, S.N., 2004, Bilayer thickness modulates the conductance of the BK channel in model membranes. Biophys. J. 86: 3620–3633.

    Article  CAS  PubMed  Google Scholar 

  • Zerangue, N., Schwappach, B., Jan, Y.N., and Jan, L.Y., 1999, A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron 22: 537–548.

    Article  CAS  PubMed  Google Scholar 

  • Zheng, Y.Z., Berg, K.B., and Foster, L.J., 2009, Mitochondria do not contain lipid rafts, and lipid rafts do not contain mitochondrial proteins. J Lipid Res. 50: 988–998.

    Google Scholar 

  • Zhou, Z., Jiang, D.J., Jia, S.J., Xiao, H.B., Xiao, B., and Li, Y.J., 2007, Down-regulation of endogenous nitric oxide synthase inhibitors on endothelial SK3 expression. Vascul. Pharmacol. 47: 265–271.

    Article  CAS  PubMed  Google Scholar 

  • Zingman, L.V., Alekseev, A.E., Hodgson-Zingman, D.M., and Terzic, A., 2007, ATP-sensitive potassium channels: metabolic sensing and cardioprotection. J. Appl. Physiol. 103: 1888–1893.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Drs. Francisco Barrantes, Olaf Andersen and Michael Tamkun for allowing us to include illustrations from their work. I also thank Dr. Barrantes and Dr. Andersen for many discussions of these topics that we had over recent years. This work was supported by NIH grants HL073965 and HL083298 for IL

Author information

Authors and Affiliations

  1. Department of Medicine, Pulmonary Section, University of Illinois at Chicago, 840 S. Wood Str, 60612, Chicago, IL, USA

    Irena Levitan

  2. Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA, USA

    Yun Fang

  3. Department of Medicine, Sections of Pulmonary, Critical Care and Sleep Medicine, University of Illinois at Chicago, 840 S Wood St, 60612, Chicago, USA

    Avia Rosenhouse-Dantsker

  4. Department of Pharmacology and Physiology, University of Rochester Medical Center, Box 711, 601 Elmwood Ave, Rochester, NY, 14642, USA

    Victor Romanenko

Authors
  1. Irena Levitan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yun Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Avia Rosenhouse-Dantsker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Victor Romanenko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Irena Levitan .

Editor information

Editors and Affiliations

  1. Hackwood Park 11, Hexham, Northumberland, NE46 1AX, United Kingdom

    J. Robin Harris

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Levitan, I., Fang, Y., Rosenhouse-Dantsker, A., Romanenko, V. (2010). Cholesterol and Ion Channels. In: Harris, J. (eds) Cholesterol Binding and Cholesterol Transport Proteins:. Subcellular Biochemistry, vol 51. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8622-8_19

Download citation

Publish with us

Policies and ethics

Search

Navigation