Abstract
Regulation of membrane potential in vascular smooth muscle cells is critical for determining the level of tone in the arterial wall and, as a result, vessel diameter and peripheral vascular resistance. K+ channels play a critical role in setting the basal level of membrane potential and in electrical and mechanical responses to changes of intraluminal pressure and vasoactive agonists. Voltage-activated K+ current (Kv) is an important component of outward K+ conductance of smooth muscle and may be divided into two varieties based on distinct inactivation characteristics: (i) rapidly inactivating, transient outward (KTO) or A-type K+ current, which exhibits rapid activation and fast, N-type inactivation kinetics, and (ii) delayed rectifier (KDR) current, which displays no, or only slow, C-type inactivation. In the past five years, it has become apparent that vascular KDR channels (i) are regulated by endogenous vasoactive molecules via phosphotransferase reactions involving serine/threonine kinases and (ii) play an important role in the control of electrical and mechanical activity, arterial diameter, and peripheral resistance. This chapter reviews our current understanding of the biophysical and pharmacological properties of vascular KDR channels, the signal transduction pathways involved in their regulation, and their possible roles in the control of tone and arterial diameter.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Adda, S., Fleischmann, B. K., Freedman, B. D., Yu, M., Hay, D. W., and Kotlikoff, M. I., 1996, Expression and function of voltage-dependent potassium channel genes in human airway smooth muscle, J. Biol. Chem. 271:13239–13243.
Aiello, E. A., Walsh, M. P., and Cole, W., 1995, Phosphorylation by protein kinase A enhances delayed rectifier K+ current in rabbit vascular smooth muscle cells, Am. J. Physiol. 268:H926–H934.
Aiello, E. A., Clément-Chomienne, O., Sontag, D. P., Walsh, M. P., and Cole, W. C., 1996, Protein kinase C inhibits delayed rectifier K+ current in rabbit vascular smooth muscle cells, Am. J. Physiol. 271:H109– H119.
Aiello, E. A., Malcolm, A. T., Walsh, M. P., and Cole, W. C., 1998, β-Adrenoceptor activation and PKA regulate delayed rectifier K+ channels of vascular smooth muscle cells, Am. J. Physiol. 275:H448–H459.
Akbarali, H. I., 1993, K+ currents in rabbit esophageal muscularis mucosae, Am. J. Physiol. 264:G1001–G1007.
Archer, S. L., 1996, Diversity of phenotype and function of vascular smooth muscle cells, J. Lab. Clin. Med. 127:524–529.
Archer, S. L, Huang, J. M. C. Reeve, H. L., Hampl, V., Tolarova, S., Michelakis, E., and Weir, E. K., 1996, Differential distribution of electrophysiologically distinct myocytes in conduit and resistance arteries determines their response to nitric oxide and hypoxia, Circ. Res. 78:431–442.
Beech, D. J., and Bolton, T. B., 1989, Two components of potassium current activated by depolarization of single smooth muscle cells from the rabbit portal vein, J. Physiol. (London) 418:293–309.
Bolzon, B. J., Xiong, Z., and Cheung, D. W., 1993, Membrane rectification in single smooth muscle cells from the rat tail artery, Pflügers Arch. 425:482–490.
Bonnet, P., Rusch, N. J., and Harder, D. R., 1991, Characterization of an outward K+ current in freshly dispersed cerebral arterial muscle cells, Pflügers Arch. 418:292–296.
Boyle, J. P., Tomasic, M., and Kotlikoff, M. I., 1992, Delayed rectifier potassium channels in canine and porcine airway smooth muscle cells, J. Physiol. (London) 447:329–350.
Brayden, J. E., 1990, Membrane hyperpolarization is a mechanism of endothelium-dependent cerebral vasodilation. Am. J. Physiol. 259:H668–H673.
Brayden, J. E., and Nelson, M. T., 1992, Regulation of arterial tone by activation of calcium-dependent potassium channels. Science 256:532–535.
Carl, A., 1995, Multiple components of delayed rectifier K+ current in canine colonic smooth muscle, J. Physiol. (London) 484:339–353.
Clément-Chomienne, O., Walsh, M. P., and Cole, W. C., 1996, Angiotensin II activation of protein kinase C decreases delayed rectifier K+ current in rabbit vascular myocytes, J. Physiol. (London) 495:689–700.
Clément-Chomienne, O., Ishii, K., Walsh, M. P., and Cole, W. C., 1999a, Identification, cloning and expression of rabbit vascular smooth muscle Kvl.5 and comparison with native delayed rectifier K+ current, J. Physiol. (London) 515:653–667.
Clément-Chomienne, O., Walsh, M. P., and Cole, W. C., 1999b, State-dependent channel block by 4-aminopyridine: Comparison of native delayed rectifier and cloned Kvl.5 currents of rabbit vascular myocytes, Biophys. J. 76:A188.
Cole, W. C., and Clément-Chomienne, O., 2000, K+ channels in smooth muscle: Structural and functional diversity, in: A View of Smooth Muscle (L. Barr, ed.), in press.
D’Angelo, G., and Meininger, G. A., 1994, Transduction mechanism involved in the regulation of myogenic activity, Hypertension 23:1096–1105.
Dong, H., Waldron, G. J., Cole, W. C., Triggle, C. R. 1998, Roles of calcium-activated and voltage-gated delayed rectifier potassium channels in endothelium-dependent vaso relaxation of the rabbit middle cerebral artery. Br. J. Pharmacol. 123(5):821–832.
Du, C., Carl, A., Smith, T. K., Sanders, K. M., and Keef, K. D., 1994, Mechanism of cyclic AMP-induced hyperpolarization in canine colon, J. Pharmacol. Exp. Ther. 268:208–215.
Edwards, G., Ibbotson, T., and Weston, A. H., 1993, Levcromakalim may induce a voltage-independent K-current in rat portal veins by modifying the gating properties of the delayed rectifier, Br. J. Pharmacol 110:1037–1048.
Edwards, G., Zygmunt, P. M., Hogestatt, E. D., and Weston, A. H., 1996, Effects of cytochrome P-450 inhibitors on potassium currents and mechanical activity in rat portal vein, Br. J. Pharmacol 119:691–701.
Evans, A. M., Osipenko, O. N., and Gurney, A. M., 1996, Properties of a novel potassium current that is active at the resting potential in rabbit pulmonary smooth muscle cells, J. Physiol. (London) 496:407–420.
Farrugia, G., 1996, Modulation of ionic currents in isolated canine and human jejunal circular smooth muscle cells by fluoxetine, Gastroenterology 110:1438–1445.
Fleischmann, B. K., Washabau, R. J., and Kotlikoff, M. I., 1993, Control of resting membrane potential by delayed rectifier potassium currents in ferret airway smooth muscle cells, J. Physiol. (L ondon) 469:625– 638.
Gelband, C. H., and Hume, J. R., 1992, Ionic currents in single smooth muscle cells of the canine renal artery, Circ. Res. 71:745–758.
Gelband, C. H., and Hume, J. R., 1995, [Ca2+]i inhibition of K+ channels in canine renal artery: Novel mechanism for agonist-induced membrane depolarization. Circ. Res. 77:121–122.
Gollasch, M., Ried, C., Bychkov, R., Luft, F. C., and Haller, H., 1996, K+ currents in human coronary artery vascular smooth muscle cells, Circ. Res. 78:676–688.
Grissmer, S., Nguyen, A. N., Aiyar, J., Hanson, D. C., Mather, R. J., Gutman, G. A., Karmilowicz, M. J., Auperin, D. D., Chandy, K. G. 1994, Pharmacological characterization of five cloned voltage-gated K+ channels, types Kvl.l, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines, Mol. Pharmacol. 45(6):1227–1234.
Halliday, F. C., Aaronson, P. I., Evans, A. M., and Gurney, A. M., 1995, The pharmacological properties of K+ currents from rabbit isolated aortic smooth muscle cells, Br. J. Pharmacol. 116:3139–3148.
Hamaguchi, M., Ishibashi, T., and Imai, S., 1992, Involvement of charybdotoxin-sensitive K+ channel in the relaxation of bovine tracheal smooth muscle by glyceryltrinitrate and sodium nitroprusside, J. Pharmacol.Exp. Ther. 262:263–270.
Hart, P. J., Overturf, K. E., Russell, S. N., Carl, A., Hume, J. R., Sanders, K. M., and Horowitz, B., 1993, Cloning and expression of a Kv1.2 class delayed rectifier K+ channel from canine colonic smooth muscle, Proc. Natl. Acad. Sci. U.S.A. 90:9659–9663.
Imamura, Y., Tomoike, H., Narishige, T., Takahashi, T., Kasuya, H., and Takeshita, A., 1992, Glibenclamide decreases basal coronary blood flow in anesthetized dogs. Am. J. Physiol. 263:H399–H404.
Ishikawa, T., Hume, J. R., and Keef, K. D., 1993, Modulation of K+ and Ca2+ channels by histamine Hi-receptor stimulation in rabbit coronary artery cells, J. Physiol. (London) 468:379–400.
Jackson, W. F., Huebner, J. M., and Rusch, N. J., 1996, Enzymatic isolation and characterization of single vascular smooth muscle cells from cremasteric arterioles, Microcirculation 3:313–328.
Karashima, T., Itoh, T., and Kuriyama, H., 1982, Effects of 2-nicotinamidoethyl nitrate on smooth muscle cells of the guinea-pig mesenteric and portal veins, J. Pharmacol. Exp. Ther. 221:472–480.
Knot, H. J., and Nelson, M. T., 1995, Regulation of membrane potential and diameter by voltage-dependent K+ channels in rabbit myogenic cerebral arteries. Am. J. Physiol. 269:H348–H355.
Knot, H. J., Zimmermann, P. A., and Nelson, M. T., 1996, Extracellular K+-induced hyperpolarizations and dilatations of rat coronary and cerebral arteries involve inward rectifier K+ channels, J. Physiol. (London) 492:419–430.
Koh, S. D., Sanders, K. M., and Carl, A., 1996, Regulation of smooth muscle delayed rectifier K+ channels by protein kinase A, Pflügers Arch. 432:401–412.
Kotlikoff, M. I., 1990, Potassium currents in canine airway smooth muscle cells, Am. J. Physiol. 259:L384– L395.
Kuriyama, H., Kitamura, K., and Nabata, H., 1995, Pharmacological and physiological significance of ion channels and factors that modulate them in vascular tissues, Pharmacol. Rev. 47:387–573.
Leblanc, N., and Chartier, D., 1998, Specific inhibitors of calmodulin-dependent protein kinase are potent blockers of voltage-dependent K+ channels in vascular myocytes, Biophys. J. 74:A111.
Leblanc, N., Wan, X., and Leung, P. M., 1994, Physiological role of Ca2+-activated and voltage-dependent K+ currents in rabbit coronary myocytes, Am. J. Physiol. 266:0523–0537.
Liu, J., Hill, M. A., and Meininger, G. A., 1994, Mechanisms of myogenic enhancement by norepinephrine, Am. J. Physiol. 266:H440–H446.
Loutzenhiser, R. D., and Parker, M. J., 1994, Hypoxia inhibits myogenic reactivity of renal afferent arterioles by activating ATP-sensitive potassium channels, Circ. Res. 74:861–869.
Mays, D. J., Foose, J. M., Philipson, L. H., and Tamkun, M. M., 1995, Localization of the Kv1.5 K+ channel protein in explanted cardiac tissue, J. Gin. Invest. 96:282–292.
Meininger, G. A., and Davis, M. J., 1992, Cellular mechanisms involved in the vascular myogenic response, Am. J. Physiol. 263:H647–H659.
Mikawa, K., Kume, H., and Takagi, K., 1997, Effects of BKCa channels on the reduction of cytosolic Ca2+ in cGMP-induced relaxation of guinea-pig trachea, clin. Exp. Pharmacol. Physiol. 24:175–181.
Neild, T. O., and Keef, K., 1985, Measurements of the membrane potential of arterial smooth muscle in anesthetized animals and its relationship to changes in artery diameter, Microvasc. Res. 30(1):19–28.
Nelson, M. T., and Quayle, J. M., 1995, Physiological roles and properties of potassium channels in arterial smooth muscle, Am. J. Physiol. 268:C799–C822.
Nelson, M. T., Patlak, J. B., Worley, J. F., and Standen, N. B., 1990, Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone, Am. J. Physiol. 259:C3–C18.
Nelson, M. T., Cheng, H., Rubart, M., Santana, L. F., Bonev, A. D., Knot, H. J., and Lederer, W. J., 1995, Relaxation of arterial smooth muscle by calcium sparks, Science 270:633–637.
Nishiyama, M., Hashitani, H., Kukuta, H., Yamomoto, Y., and Suzuki, H., 1998, Potassium channels activated in the endothelium-dependent hyperpolarization in guinea-pig coronary artery, J. Physiol. (London) 510:455–465.
Okabe, K., Kitamura, K., and Kuriyama, H., 1987, Features of 4-aminopyridine sensitive outward current observed in single smooth muscle cells from the rabbit pulmonary artery, Pflügers Arch. 409:561–568.
Osipenko, O. N., Evans, A. M., and Gurney, A. M., 1997, Regulation of resting potential of rabbit pulmonary artery myocytes by a low threshold, O2-sensing potassium current, Br. J. Pharmacol 120:1461–1470.
Overturf, K. E., Russell, S. N., Carl, A., Vogalis, F., Hart, P. J., Hume, J. R., Sanders, K. M., and Horowitz, B., 1994, Cloning and characterization of a Kv1.5 delayed rectifier K+ channel from vascular and visceral smooth muscles. Am. J. Physiol. 267:0231–0238.
Patel, A. J., Lazdunski, M., and Honore, E., 1997, Kv2.1/Kv9.3, a novel ATP-dependent delayed-rectifier K+ channel in oxygen-sensitive pulmonary artery myocytes, EMBO J. 16:6615–6625.
Perez, G. J., Bonev, A. D., Patlak, J. B., and Nelson, M. T., 1999, Functional coupling of ryanodine receptors to KCa channels in smooth muscle cells from rat cerebral arteries, J. Gen. Physiol. 113:229–238.
Pfrunder, D., and Kreye, V. A., 1992, Tedisamil inhibits the delayed rectifier K+ current in single smooth muscle cells of the guinea-pig portal vein, Pflügers Arch. 421:22–25.
Post, J. M., Gelband, C. H., and Hume, J. R., 1995, [Ca2+]i inhibition of K+ channels in canine pulmonary artery: Novel mechanism for hypoxia-induced membrane depolarization, Grc. Res. 77:131–139.
Quayle, J. M., McCarron, J. G., Brayden, J. E., and Nelson, M. T., 1993, Inward rectifier K+ currents in smooth muscle cells from rat resistance-sized cerebral arteries, Am. J. Physiol. 265:0363–0370.
Rettig, J., Heinemann, S. H., Wunder, F., Lorra, C., Parcei, D. N., Dolly, J. O., and Pongs, O., 1992, Inactivation properties of voltage-gated K+ channels altered by presence of β-subunit, Nature 369:289–294.
Rhodes, K. J., Monaghan, M. M., Barrezueta, N. X., Nawoschik, S., Bekele-Arcuri, Z, Matos, M. F., Nakahira, K., Schechter, L. E., and Trimmer, J. S., 1996, Voltage-gated K+ channel β subunits: Expression and distribution of Kvβ1 and Kvβ2 in adult rat brain, J. Neurosci. 16:4846–4860.
Roberds. S. L., and Tamkun, M. M., 1991, Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart, Proc. Natl. Acad. Sci. U.S.A. 88:1798–1802.
Salter, K. J., and Kozlowski, R. Z., 1996, Endothelin receptor coupling to potassium and chloride channels in isolated rat pulmonary arterial myocytes, J. Pharmacol. Exp. Ther. 279:1053–1062.
Salter, K. J., Wilson, C. M., Kato, K., and Kozlowski, R. Z., 1998, Endothelin-1, delayed rectifier K channels, and pulmonary arterial smooth muscle, J. Cardiovasc. Pharmacol. 31(Suppl 1):S81–S83.
Schmalz, F., Kinsella, J., Koh, S. D., Vogalis, F., Schneider, A., Flynn, E. R., Kenyon, J. L., and Horowitz, B., 1998, Molecular identification of a component of delayed rectifier current in gastrointestinal smooth muscles, Am. J. Physiol. 274:G901–G911.
Shimizu, S., and Paul, R. J., 1997, The endothelium-dependent, substance P relaxation of porcine coronary arteries resistant to nitric oxide synthesis inhibition is partially mediated by 4-aminopyridine-sensitive voltage-dependent K+ channels, Endothelium 5:287–295.
Shimoda, L. A., Sylvester, J. T., and Sham, J. S., 1998, Inhibition of voltage-gated K+ current in rat intrapulmonary arterial myocytes by endothelin-1, Am. J. Physiol. 274:L842–L853.
Shuttleworth, C. W., Koh, S. D., Bayginov, O., and Sanders, K. M., 1996, Activation of delayed rectifier potassium channels in canine proximal colon by vasoactive intestinal peptide, J. Physiol. (London) 493:651–663.
Smirnov, S. V., and Aaronson, P. I., 1992, Ca2+-activated and voltage-gated K+ currents in smooth muscle cells isolated from human mesenteric arteries, J. Physiol. (London) 457:431–454.
Smirnov, S. V., and Aaronson, P. I., 1995, Inhibition of vascular smooth muscle cell K+ currents by tyrosine kinase inhibitors genistein and ST 638, Circ. Res. 76:310–316.
Smirnov, S. V., Robertson, T. P., Ward, J. P., and Aaronson, P. I., 1994, Chronic hypoxia is associated with reduced delayed rectifier K+ current in rat pulmonary artery muscle cells, Am. J. Physiol. 266:H365–H370.
Snetkov, V. A., Hirst, S. J., Twort, C. H. C., and Ward, J. P. T., 1995, Potassium currents in human freshly isolated bronchial smooth muscle cells, Br. J. Pharmacol. 115:1117–1125.
Sobey, C. G., and Faraci, F. M., 1999, Role of voltage-dependent K+ channels and soluble guanylate cyclase in dilator responses of the basilar artery to nitric oxide, Br. J. Pharmacol. 126(6):1437–1443.
Sturek, M., Stehno-Bittel, L., and Obye, P., 1991, Modulation of ion channels by calcium release in coronary artery smooth muscle, in: Ion Channels of Vascular Smooth Muscle Cells and Endothelial Cells (N. Sperelakis, and H. Kuriyama, eds.), Elsevier, New York pp. 65–80.
Taguchi, H., Heistad, D. D., Kitazono, T., and Faraci, F. M., 1995, Dilatation of cerebral arterioles in response to activation of adenylate cyclase is dependent on activation of Ca2+-dependent K+ channels, Circ. Res. 76:1057–1062.
Tamkun, M. M., Bennett, P. B., and Snyders, D. J., 1995, Cloning and expression of human cardiac potassium channels, in: Cardiac Electrophysiology. From Cell to Bedside (D. P. Zipes and J. Jalife, eds.), Sanders, Philadelphia pp. 21–31.
Taniguchi, J., Furukawa, K. I., and Shigekawa, M., 1993, Maxi K+ channels are stimulated by cyclic guanosine monophosphate-dependent protein kinase in canine coronary artery smooth muscle cells, Pflügers Arch. 423:167–172.
Tare, M., Parkington, H. C., Coleman, H. A., Neild, T. O., and Dusting, G. J., 1990, Hyperpolarization and relaxation of arterial smooth muscle caused by nitric oxide derived from the endothelium, Nature 346:69–71.
Thornbury, K. D., Ward, S. M., and Sanders, K. M., 1992, Participation of fast-acting, voltage-dependent K currents in electrical slow waves of colonic circular muscle, Am. J. Physiol. 263:C226–C236.
Volk, K. A., Shibata, E. F., 1993, Single delayed rectifier potassium channels from rabbit coronary artery myocytes. Am. J. Physiol. 264(4pt 2):H1146–1153.
Volk, K. A., Matsuda, J. J., and Shibata, E. F., 1991, A voltage-dependent potassium current in rabbit coronary artery smooth muscle cells, J. Physiol. (London) 439:751–768.
Waldron, G. J., and Cole, W. C, 1999, Activation of vascular smooth muscle K+ channels by endotheliumderived relaxing factors, Clin. Exp. Pharmacol. Physiol. 26:180–184.
Waldron, G. J., Iftinca, M., Clément-Chomienne, O., Triggle, C. R., and Cole, W. C, 1999, Direct block of voltage-gated K+ current of vascular myocytes by clotrimazole not involving inhibition of cytochrome P450, Biophys. J. 76:A188.
Walsh, M. P., 1994, Regulation of vascular smooth muscle tone, Can. J. Physiol. Pharmacol. 72:919–936.
Wang, H., Mori, Y., and Koren, G., 1994, Expression of Kvl.5 in the rat tissues and the mechanism of cell specific regulation of Kvl.5 gene by cAMP, Biophys. J. 66:207A.
Wang, J., Juhaszova, M., Rubin, L. J., and Yuan, X. J., 1997, Hypoxia inhibits gene expression of voltage-gated K+ channel alpha subunits in pulmonary artery smooth muscle cells, J. Clin. Invest. 100:2347–2353.
Weir, E. K., Reeve, H. L., Huang, J. M. C., Michelakis, E., Nelson, D. P., Hampl, V., and Archer, S. L., 1996, Anorexic agents aminorex, fenfluramine, and dexfenfluramine inhibit potassium current in rat pulmonary vascular smooth muscle and cause pulmonary vasoconstriction, Circulation 94:2216–2220.
Xiong, Z., Sperelakis, N., NofFsinger, A., and Fenoglio-Preiser, A., 1995, Potassium currents in rat colonic smooth muscle cells and changes during development and aging, Pflügers Arch. 430:563–572.
Yuan, X.-J., 1995, Voltage-gated K+ currents regulate resting membrane potential and [Ca2+]i in pulmonary arterial myocytes, Circ. Res. 77:370–378.
Yuan, X.-J., Tod, M. L., Rubin, L. J., and Blaustein, M. P., 1995, Inhibition of cytochrome P-450 reduces voltage-gated K+ currents in pulmonary arterial myocytes, Am. J. Physiol. 268:C259–C270.
Yuan, X.-J., Tod, M. L., Rubin, L. J., and Blaustein, M. P., 1996, NO hyperpolarizes pulmonary artery smooth muscle cells and decreases the intracellular Ca2+ concentration by activating voltage-gated K+ channels, Proc. Natl. Acad. Sci. U.S.A. 93:10489–10494.
Yuan, X. J., Wang, J., Juhaszova, M., Golovina, V. A., and Rubin, L. J., 1998, Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells. Am. J. Physiol. 274:L621– L635.
Zhang, L., Bonev, A. D., Nelson, M. T., and Mawe, G. M., 1993, Ionic basis of the action potential of guinea pig gallbladder smooth muscle cells, Am. J. Physiol. 265:C1552–C1561.
Zhao, Y. J., Wang, J., Rubin, L. J., and Yuan, X. J., 1997, Inhibition of K(V) and K(Ca) channels antagonizes NO-induced relaxation in pulmonary artery, Am. J. Physiol. 272:H904–H912.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer Science+Business Media New York
About this chapter
Cite this chapter
Cole, W.C., Walsh, M.P. (2001). Delayed Rectifier K+Channels of Vascular Smooth Muscle: Characterization, Function, and Regulation by Phosphorylation. In: Archer, S.L., Rusch, N.J. (eds) Potassium Channels in Cardiovascular Biology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1303-2_24
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1303-2_24
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5487-1
Online ISBN: 978-1-4615-1303-2
eBook Packages: Springer Book Archive