Advertisement

Synchronization Modulation of Na/K Pumps Induced Membrane Potential Hyperpolarization in Both Physiological and Hyperkalemic Conditions

  • Pengfei Liang
  • Jason Mast
  • Wei ChenEmail author
Article
  • 18 Downloads

Abstract

The capability of the synchronization modulation (SM) technique in enhancing the function of Na/K pumps has been demonstrated in various cells and tissues, including cardiomyocytes, a monolayer of cultured MDCK kidney cells, peripheral blood vessels, and frog skeletal muscles. This study characterized the membrane potential hyperpolarization induced by SM in both physiological and high [K+]o conditions on single skeletal muscle fibers. The results showed that SM could consistently induce membrane potential hyperpolarization by a few millivolts, and this hyperpolarization was not possible in the presence of ouabain. In contrast, the same electrical pulses but with random frequencies, constant frequencies, or synchronization with backward-modulation could not hyperpolarize the membrane potential. Prolonged field application and higher field intensity enhanced the effects of SM-induced hyperpolarization. Finally, the effect of SM was tested on skeletal muscle fibers incubated in a solution with high external potassium. Results showed that the SM electric field could hyperpolarize the membrane potential even if the external K+ concentration was higher than the normal, which implied the therapeutic effects of the SM electric field on the hyperkalemic situation.

Keywords

Synchronization modulation Membrane potential hyperpolarization Hyperkalemia Na/K pump 

Notes

Author Contributions

PL conducted all of the experiments and data analysis; JM developed SM pulse generator with Java program; Dr. WC developed and patented the SM technique and supervised the project.

Funding

This project was partially supported by NIH Grant No. 2R01 50785 (W.C.) and NSF Grant No. 0515787(W.C.).

Compliance with Ethical Standards

Conflict of interest

Wei Chen has a patent on the SM technique. The other authors have no conflicts of interest to declare.

References

  1. Amaranath L, Andersen NB (1976) The effect of general anesthetic agents, ouabain, and aldosterone on striated muscle contraction in toad. Anesth Analg 55(3):409–414.  https://doi.org/10.4000/histoiremesure.137 Google Scholar
  2. Barlow CW, Qayyum MS, Davey PP, Conway J, Paterson DJ, Robbins PA (1994) Effect of physical training on exercise-induced hyperkalemia in chronic heart failure relation with ventilation and catecholamines. Circluation 89(3):1144–1152Google Scholar
  3. Benders AAGM, Wevers RA, Veerkamp JH (1996) Ion transport in human skeletal muscle cells: disturbances in myotonic dystrophy and Brody’s disease. Acta Physiol Scand 156(3):355–367.  https://doi.org/10.1046/j.1365-201X.1996.202000.x Google Scholar
  4. Blank M (1987) Theory of frequency-dependent ion concentration changes in oscillating electric fields. J Electrochem Soc 134(5):1112–1117Google Scholar
  5. Buchanan R, Nielsen OB, Clausen T (2002) Excitation- and beta(2)-agonist-induced activation of the Na(+)-K(+) pump in rat soleus muscle. J Physiol 545(Pt 1):229–240.  https://doi.org/10.1113/JPHYSIOL.2002.023325 Google Scholar
  6. Chen W (2008) Synchronization of ion exchangers by an oscillating electric field: theory synchronization of ion exchangers by an oscillating electric field: theory. J Phys Chem B 112(July):10064–10070.  https://doi.org/10.1021/jp0754637 Google Scholar
  7. Chen W, Huang F (2008) Computer simulation of synchronization of Na/K pump molecules. J Bioenerg Biomembr 40(4):337–345.  https://doi.org/10.1007/s10863-008-9152-z Google Scholar
  8. Chen W, Lee RC (1994) An improved double vaseline gap voltage clamp to study electroporated skeletal muscle fibers. Biophys J 66:700–709Google Scholar
  9. Chen W, Chiu A, Hui S (1991) Differential blockage of charge movement components in frog cut twitch fibres by nifedipine. J Physiol 444:579–603Google Scholar
  10. Chen W, Zhang Z, Huang F (2007) Entrainment of Na/K pumps by a synchronization modulation electric field. J Bioenerg Biomembr 39(4):331–339.  https://doi.org/10.1007/s10863-007-9096-8 Google Scholar
  11. Chen W, Zhang Z, Huang F (2008) Synchronization of Na/K pump molecules by an oscillating electric field. J Bioenerg Biomembr 40(4):347–357.  https://doi.org/10.1007/s10863-008-9150-1 Google Scholar
  12. Cheng C-J, Kuo E, Huang C-L (2013) Extracellular potassium homeostasis: insights from hypokalemic periodic paralysis. Semin Nephrol 33(3):237–247.  https://doi.org/10.1016/j.semnephrol.2013.04.004 Google Scholar
  13. Clausen T (2003) Na+-K+ pump regulation and skeletal muscle contractility. Physiol Rev 83(4):1269–1324.  https://doi.org/10.1152/physrev.00011.2003 Google Scholar
  14. Clausen T (2008) Role of Na+, K+-pumps and transmembrane Na+, K+ -distribution in muscle function: the FEPS Lecture - Bratislava 2007. Acta Physiol 192(3):339–349.  https://doi.org/10.1111/j.1748-1716.2007.01798.x Google Scholar
  15. Clausen T (2013) Quantification of Na+, K+ pumps and their transport rate in skeletal muscle: functional significance. J Gen Physiol 142(4):327–345.  https://doi.org/10.1085/jgp.201310980 Google Scholar
  16. Clausen T, Nielsen OB (2007) Potassium, Na+, K+-pumps and fatigue in rat muscle. J Physiol 584(1):295–304.  https://doi.org/10.1113/jphysiol.2007.136044 Google Scholar
  17. Clausen T, Overgaard K (2000) The role of K+ channels in the force recovery elicited by Na+-K+ pump stimulation in Ba2+-paralysed rat skeletal muscle. J Physiol 527(2):325–332.  https://doi.org/10.1111/j.1469-7793.2000.00325.x Google Scholar
  18. Clausen T, Overgaard K, Nielsen OB (2004) Evidence that the Na+-K+ leak/pump ratio contributes to the difference in endurance between fast- and slow-twitch muscles. Acta Physiol Scand 180(2):209–216.  https://doi.org/10.1111/j.0001-6772.2003.01251.x Google Scholar
  19. Clausen T, Nielsen OB, Clausen JD, Pedersen TH, Hayward LJ (2011) Na+, K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis. J Gen Physiol 138(1):117–130.  https://doi.org/10.1085/jgp.201010586 Google Scholar
  20. Clay JR, Shlesinger MF (1984) Analysis of the effects of cesium ions on potassium channel currents in biological membranes. J Theor Biol 107(2):189–201Google Scholar
  21. Dando R, Fang Z, Chen W (2012) Hyperpolarization of the membrane potential in cardiomyocyte tissue slices by the synchronization modulation electric field. J Membr Biol 245(2):97–105.  https://doi.org/10.1007/s00232-012-9418-6 Google Scholar
  22. de Paoli FV, Overgaard K, Pedersen TH, Nielsen OB (2007) Additive protective effects of the addition of lactic acid and adrenaline on excitability and force in isolated rat skeletal muscle depressed by elevated extracellular K+. J Physiol 581(2):829–839.  https://doi.org/10.1113/jphysiol.2007.129049 Google Scholar
  23. Desnuelle C, Lombet A, Serratrice G, Lazdunski M (1982) Sodium channel and sodium pump in normal and pathological muscles from patients with myotonic muscular dystrophy and lower motor neuron impairment. J Clin Investig 69(2):358–367.  https://doi.org/10.1172/JCI110459 Google Scholar
  24. Green S, Langberg H, Skovgaard D, Bülow J, Kjaer M (2000a) Interstitial and arterial-venous [K+] in human calf muscle during dynamic exercise: effect of ischaemia and relation to muscle pain. J Physiol 529(3):849–861.  https://doi.org/10.1111/j.1469-7793.2000.00849.x Google Scholar
  25. Green S, Langberg H, Skovgaard D, Bülow J, Kjær M (2000b) Interstitial and arterial-venous [K+] in human calf muscle during dynamic exercise: effect of ischaemia and relation to muscle pain. J Physiol 529(3):849–861.  https://doi.org/10.1111/j.1469-7793.2000.00849.x Google Scholar
  26. Gruener R, Stern LZ, Markovitz D, Gerdes C (1979) Electrophysiologic properties of intercostal muscle fibers in human neuromuscular diseases. Muscle Nerve 2(3):165–172.  https://doi.org/10.1002/mus.880020303 Google Scholar
  27. Hallén J, Gullestad L, Sejersted OM (1994) K+ shifts of skeletal muscle during stepwise bicycle exercise with and without beta-adrenoceptor blockade. J Physiol 477(1):149–159.  https://doi.org/10.1113/jphysiol.1994.sp020179 Google Scholar
  28. Haller RG, Clausen T, Vissing J (1998) Reduced levels of skeletal muscle Na+K+-ATPase in McArdle disease. Neurology 50(1):37–40Google Scholar
  29. Huang F, Rabson D, Chen W (2009) Distribution of the Na/K pumps’ turnover rates as a function of membrane potential, temperature, and ion concentration gradients and effect of fluctuations. J Phys Chem B 113(23):8096–8102.  https://doi.org/10.1021/jp8054153 Google Scholar
  30. Juel C, Pilegaard H, Nielsen JJ, Bangsbo J (2000) Interstitial K+ in human skeletal muscle during and after dynamic graded exercise determined by microdialysis. Am J Physiol-Regul Integr Comp Physiol 278(2):R400–R406.  https://doi.org/10.1152/ajpregu.2000.278.2.R400 Google Scholar
  31. Kirsch GE, Narahashi T (1978) 3,4-Diaminopyridine. A potent new potassium channel blocker. Biophys J 22(3):507–512.  https://doi.org/10.1016/S0006-3495(78)85503-9 Google Scholar
  32. Lehnhardt A, Kemper MJ (2011) Pathogenesis, diagnosis and management of hyperkalemia. Pediatr Nephrol (Berlin, Germany) 26(3):377–384.  https://doi.org/10.1007/s00467-010-1699-3 Google Scholar
  33. Medbø JI, Sejersted OM (1990) Plasma potassium changes with high intensity exercise. J Physiol 421(1):105–122.  https://doi.org/10.1113/jphysiol.1990.sp017935 Google Scholar
  34. Nørgaard A, Bjerregaard P, Baandrup U, Kjeldsen K, Reske-Nielsen E, Thomsen PE (1990) The concentration of the Na, K-pump in skeletal and heart muscle in congestive heart failure. Int J Cardiol 26(2):185–190Google Scholar
  35. Overgaard K, Nielsen OB (2001) Activity-induced recovery of excitability in K-depressed rat soleus muscle. Am J Physiol-Regul Integr Comp Physiol 280:R48–R55Google Scholar
  36. Pirkmajer S, Chibalin AV (2016) Na, K-ATPase regulation in skeletal muscle. Am J Physiol-Endocrinol Metab 311(1):E1–E31.  https://doi.org/10.1152/ajpendo.00539.2015 Google Scholar
  37. Sejersted OM, Sjøgaard G (2000) Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise. Physiol Rev 80(4):1411–1481.  https://doi.org/10.1152/physrev.2000.80.4.1411 Google Scholar
  38. Senatorov VV, Stys PK, Hu B (2004) Regulation of Na+, K+-ATPase by persistent sodium accumulation in adult rat thalamic neurones. J Physiol.  https://doi.org/10.1111/j.1469-7793.2000.00343.x Google Scholar
  39. Serpersu EH, Tsong TY (1983) Stimulation of ouabain-sensitive Rb+ uptake in human erothrocytes with an external electric field. J Membr Biol 74(3):191–201Google Scholar
  40. Tran V, Zhang X, Cao L, Li H, Lee B, So M et al (2013) Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K Pumps. PLoS ONE.  https://doi.org/10.1371/journal.pone.0061509 Google Scholar
  41. Tsong TY (1991) Electroporation of cell membranes. Biophys J 60(2):297–306.  https://doi.org/10.1016/S0006-3495(91)82054-9 Google Scholar
  42. Tsong TY, Astumian D (1987) Electroconformational coupling and membrane protein function. Prog Biophy Mol Bio 50(1):1–45Google Scholar
  43. Weaver JC (1993) Electroporation: a general phenomenon for manipulating cells and tissues. J Cell Biochem 51(4):426–435Google Scholar
  44. Xie TD, Chen Y, Tsong TY, Kong Urlisi of Scin H, Bay CW, Kong H (1994) Recognition and processing of randomly fluctuating eletric signals by Na, K-ATPase. Biophys J 67:1247–1251.  https://doi.org/10.1016/S0006-3495(94)80594-6 Google Scholar
  45. Zhang L, Fang Z, Chen W (2012) Quick and effective hyperpolarization of the membrane potential in intact smooth muscle cells of blood vessels by synchronization modulation electric field. J Bioenerg Biomembr 44(3):385–395.  https://doi.org/10.1007/s10863-012-9432-5 Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Physics, Cellular and Molecular Biophysics LabUniversity of South FloridaTampaUSA

Personalised recommendations