Skip to main content
PMC home page
The Journal of General Physiology logoLink to The Journal of General Physiology
. 1988 May 1;91(5):641–657. doi: 10.1085/jgp.91.5.641

Hydrogen ion modulation of Ca channel current in cardiac ventricular cells. Evidence for multiple mechanisms

PMCID: PMC2216148  PMID: 2458428

Abstract

We have investigated the effects of H ions on (L-type) Ca channel current in isolated ventricular cells. We find that the current amplitude is enhanced in solutions that are alkaline relative to pH 7.4 and reduced in solutions acidic to this pH. We measured pH0-induced shifts in channel gating and analyzed our results in terms of surface potential theory. The shifts are well described by changes in surface potential caused by the binding of H ions to negative charges on the cell surface. The theory predicts a pK of 5.8 for this binding. Gating shifts alone cannot explain all of our observations on modulation of current amplitude. Our results suggest that an additional mechanism contributes to modification of the current amplitude.

Full Text

The Full Text of this article is available as a PDF (926.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bean B. P. Two kinds of calcium channels in canine atrial cells. Differences in kinetics, selectivity, and pharmacology. J Gen Physiol. 1985 Jul;86(1):1–30. doi: 10.1085/jgp.86.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Begenisich T., Danko M. Hydrogen ion block of the sodium pore in squid giant axons. J Gen Physiol. 1983 Nov;82(5):599–618. doi: 10.1085/jgp.82.5.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Begenisich T. Magnitude and location of surface charges on Myxicola giant axons. J Gen Physiol. 1975 Jul;66(1):47–65. doi: 10.1085/jgp.66.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown R. H., Jr, Noble D. Displacement of activator thresholds in cardiac muscle by protons and calcium ions. J Physiol. 1978 Sep;282:333–343. doi: 10.1113/jphysiol.1978.sp012466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Campbell D. T., Hille B. Kinetic and pharmacological properties of the sodium channel of frog skeletal muscle. J Gen Physiol. 1976 Mar;67(3):309–323. doi: 10.1085/jgp.67.3.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carbone E., Testa P. L., Wanke E. Intracellular pH and ionic channels in the Loligo vulgaris giant axon. Biophys J. 1981 Aug;35(2):393–413. doi: 10.1016/S0006-3495(81)84798-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chesnais J. M., Coraboeuf E., Sauviat M. P., Vassas J. M. Sensitivity to H, Li and Mg ions of the slow inward sodium current in frog atrial fibres. J Mol Cell Cardiol. 1975 Sep;7(9):627–642. doi: 10.1016/0022-2828(75)90140-6. [DOI] [PubMed] [Google Scholar]
  8. Dani J. A. Ion-channel entrances influence permeation. Net charge, size, shape, and binding considerations. Biophys J. 1986 Mar;49(3):607–618. doi: 10.1016/S0006-3495(86)83688-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ellis D., MacLeod K. T. Sodium-dependent control of intracellular pH in Purkinje fibres of sheep heart. J Physiol. 1985 Feb;359:81–105. doi: 10.1113/jphysiol.1985.sp015576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fabiato A., Fabiato F. Calcium and cardiac excitation-contraction coupling. Annu Rev Physiol. 1979;41:473–484. doi: 10.1146/annurev.ph.41.030179.002353. [DOI] [PubMed] [Google Scholar]
  11. Farmer B. B., Mancina M., Williams E. S., Watanabe A. M. Isolation of calcium tolerant myocytes from adult rat hearts: review of the literature and description of a method. Life Sci. 1983 Jul 4;33(1):1–18. doi: 10.1016/0024-3205(83)90706-3. [DOI] [PubMed] [Google Scholar]
  12. Fozzard H. A. Heart: excitation-contraction coupling. Annu Rev Physiol. 1977;39:201–220. doi: 10.1146/annurev.ph.39.030177.001221. [DOI] [PubMed] [Google Scholar]
  13. Gaskell W. H. On the Tonicity of the Heart and Blood Vessels. J Physiol. 1880 Aug;3(1):48–92.16. doi: 10.1113/jphysiol.1880.sp000083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gilly W. F., Armstrong C. M. Divalent cations and the activation kinetics of potassium channels in squid giant axons. J Gen Physiol. 1982 Jun;79(6):965–996. doi: 10.1085/jgp.79.6.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gilly W. F., Armstrong C. M. Slowing of sodium channel opening kinetics in squid axon by extracellular zinc. J Gen Physiol. 1982 Jun;79(6):935–964. doi: 10.1085/jgp.79.6.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hagiwara S., Miyazaki S., Moody W., Patlak J. Blocking effects of barium and hydrogen ions on the potassium current during anomalous rectification in the starfish egg. J Physiol. 1978 Jun;279:167–185. doi: 10.1113/jphysiol.1978.sp012338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  18. Hess P., Lansman J. B., Tsien R. W. Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel current in ventricular heart cells. J Gen Physiol. 1986 Sep;88(3):293–319. doi: 10.1085/jgp.88.3.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hille B., Woodhull A. M., Shapiro B. I. Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH. Philos Trans R Soc Lond B Biol Sci. 1975 Jun 10;270(908):301–318. doi: 10.1098/rstb.1975.0011. [DOI] [PubMed] [Google Scholar]
  20. Hutter O. F., Warner A. E. The pH sensitivity of the chloride conductance of frog skeletal muscle. J Physiol. 1967 Apr;189(3):403–425. doi: 10.1113/jphysiol.1967.sp008176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Iijima T., Ciani S., Hagiwara S. Effects of the external pH on Ca channels: experimental studies and theoretical considerations using a two-site, two-ion model. Proc Natl Acad Sci U S A. 1986 Feb;83(3):654–658. doi: 10.1073/pnas.83.3.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Irisawa H., Sato R. Intra- and extracellular actions of proton on the calcium current of isolated guinea pig ventricular cells. Circ Res. 1986 Sep;59(3):348–355. doi: 10.1161/01.res.59.3.348. [DOI] [PubMed] [Google Scholar]
  23. Kass R. S., Krafte D. S. Negative surface charge density near heart calcium channels. Relevance to block by dihydropyridines. J Gen Physiol. 1987 Apr;89(4):629–644. doi: 10.1085/jgp.89.4.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kass R. S. Nisoldipine: a new, more selective calcium current blocker in cardiac Purkinje fibers. J Pharmacol Exp Ther. 1982 Nov;223(2):446–456. [PubMed] [Google Scholar]
  25. Kohlhardt M., Haap K., Figulla H. R. Influence of low extracellular pH upon the Ca inward current and isometric contractile force in mammalian ventricular myocardium. Pflugers Arch. 1976 Oct 15;366(1):31–38. doi: 10.1007/BF02486557. [DOI] [PubMed] [Google Scholar]
  26. Kurachi Y. The effects of intracellular protons on the electrical activity of single ventricular cells. Pflugers Arch. 1982 Sep;394(3):264–270. doi: 10.1007/BF00589102. [DOI] [PubMed] [Google Scholar]
  27. Matsuda H., Noma A. Isolation of calcium current and its sensitivity to monovalent cations in dialysed ventricular cells of guinea-pig. J Physiol. 1984 Dec;357:553–573. doi: 10.1113/jphysiol.1984.sp015517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McDonald T. F. The slow inward calcium current in the heart. Annu Rev Physiol. 1982;44:425–434. doi: 10.1146/annurev.ph.44.030182.002233. [DOI] [PubMed] [Google Scholar]
  29. Mitra R., Morad M. A uniform enzymatic method for dissociation of myocytes from hearts and stomachs of vertebrates. Am J Physiol. 1985 Nov;249(5 Pt 2):H1056–H1060. doi: 10.1152/ajpheart.1985.249.5.H1056. [DOI] [PubMed] [Google Scholar]
  30. Nilius B., Hess P., Lansman J. B., Tsien R. W. A novel type of cardiac calcium channel in ventricular cells. Nature. 1985 Aug 1;316(6027):443–446. doi: 10.1038/316443a0. [DOI] [PubMed] [Google Scholar]
  31. Ohmori H., Yoshii M. Surface potential reflected in both gating and permeation mechanisms of sodium and calcium channels of the tunicate egg cell membrane. J Physiol. 1977 May;267(2):429–463. doi: 10.1113/jphysiol.1977.sp011821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Piwnica-Worms D., Jacob R., Horres C. R., Lieberman M. Na/H exchange in cultured chick heart cells. pHi regulation. J Gen Physiol. 1985 Jan;85(1):43–64. doi: 10.1085/jgp.85.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Prod'hom B., Pietrobon D., Hess P. Direct measurement of proton transfer rates to a group controlling the dihydropyridine-sensitive Ca2+ channel. Nature. 1987 Sep 17;329(6136):243–246. doi: 10.1038/329243a0. [DOI] [PubMed] [Google Scholar]
  34. Reuter H. A variety of calcium channels. Nature. 1985 Aug 1;316(6027):391–391. doi: 10.1038/316391a0. [DOI] [PubMed] [Google Scholar]
  35. Reuter H. Properties of two inward membrane currents in the heart. Annu Rev Physiol. 1979;41:413–424. doi: 10.1146/annurev.ph.41.030179.002213. [DOI] [PubMed] [Google Scholar]
  36. Sato R., Noma A., Kurachi Y., Irisawa H. Effects of intracellular acidification on membrane currents in ventricular cells of the guinea pig. Circ Res. 1985 Oct;57(4):553–561. doi: 10.1161/01.res.57.4.553. [DOI] [PubMed] [Google Scholar]
  37. Schauf C. L., Davis F. A. Sensitivity of the sodium and potassium channels of Myxicola giant axons to changes in external pH. J Gen Physiol. 1976 Feb;67(2):185–195. doi: 10.1085/jgp.67.2.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sheu S. S., Sharma V. K., Banerjee S. P. Measurement of cytosolic free calcium concentration in isolated rat ventricular myocytes with quin 2. Circ Res. 1984 Dec;55(6):830–834. doi: 10.1161/01.res.55.6.830. [DOI] [PubMed] [Google Scholar]
  39. Shrager P. Ionic conductance changes in voltage clamped crayfish axons at low pH. J Gen Physiol. 1974 Dec;64(6):666–690. doi: 10.1085/jgp.64.6.666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Vogel S., Sperelakis N. Blockade of myocardial slow inward current at low pH. Am J Physiol. 1977 Sep;233(3):C99–103. doi: 10.1152/ajpcell.1977.233.3.C99. [DOI] [PubMed] [Google Scholar]
  41. Yatani A., Goto M. The effect of extracellular low pH on the plateau current in isolated, single rat ventricular cells--a voltage clamp study. Jpn J Physiol. 1983;33(3):403–415. doi: 10.2170/jjphysiol.33.403. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of General Physiology are provided here courtesy of The Rockefeller University Press

RESOURCES