Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1983 May;338:321–337. doi: 10.1113/jphysiol.1983.sp014675

Modulation by intracellular ATP and cyclic AMP of the slow inward current in isolated single ventricular cells of the guinea-pig.

H Irisawa, S Kokubun
PMCID: PMC1197196  PMID: 6308246

Abstract

Effects of ATP and of cyclic AMP on membrane current systems were investigated in isolated single ventricular cells from guinea-pig hearts by applying the suction electrode method. The intracellular milieu was dialysed with various solutions which were perfused continuously through the suction pipette. The presence of ATP, cyclic AMP and EGTA in the perfusion solution kept the plateau phase of the action potential almost intact for as long as 30 min. With depolarizing voltage-clamp pulses from holding potentials between -30 and -40 mV, the slow inward current (isi) was activated at potentials positive to -20 mV. The inactivation time course of isi was fitted by two exponential components in the potential range between -10 mV and +30 mV. By increasing ATP from 2 to 9.5 mM in the solution, the amplitude of isi was increased and the slow component of inactivation was accelerated. The steady-state current-voltage relationship (I-V curve), exhibited a negative slope that became steeper after increasing the ATP concentration. The current was shifted towards the outward direction between -40 mV and -10 mV and became more inward between -10 mV and +40 mV. Increase of the cyclic AMP concentration from 30 to 60 microM also enhanced the amplitude of isi, but the negative slope in the steady-state I-V curve was unaffected. Assuming that the concentration of free Ca2+ in the cell was well buffered at a low level by the EGTA-Ca buffer solution in the pipette, it was concluded that [ATP]i and [cyclic AMP]i exert a direct influence on membrane current systems of the ventricular cell.

Full text

PDF
321

Selected References

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

  1. Beeler G. W., Jr, Reuter H. Membrane calcium current in ventricular myocardial fibres. J Physiol. 1970 Mar;207(1):191–209. doi: 10.1113/jphysiol.1970.sp009056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown A. M., Lee K. S., Powell T. Sodium current in single rat heart muscle cells. J Physiol. 1981 Sep;318:479–500. doi: 10.1113/jphysiol.1981.sp013879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown A. M., Lee K. S., Powell T. Voltage clamp and internal perfusion of single rat heart muscle cells. J Physiol. 1981 Sep;318:455–477. doi: 10.1113/jphysiol.1981.sp013878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown A. M., Morimoto K., Tsuda Y., wilson D. L. Calcium current-dependent and voltage-dependent inactivation of calcium channels in Helix aspersa. J Physiol. 1981 Nov;320:193–218. doi: 10.1113/jphysiol.1981.sp013944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Byerly L., Hagiwara S. Calcium currents in internally perfused nerve cell bodies of Limnea stagnalis. J Physiol. 1982 Jan;322:503–528. doi: 10.1113/jphysiol.1982.sp014052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carmeliet E. Cardiac transmembrane potentials and metabolism. Circ Res. 1978 May;42(5):577–587. doi: 10.1161/01.res.42.5.577. [DOI] [PubMed] [Google Scholar]
  7. Clark M. G., Gannon B. J., Bodkin N., Patten G. S., Berry M. N. An improved procedure for the high-yield preparation of intact beating heart cells from the adult rat biochemical and morphologic study. J Mol Cell Cardiol. 1978 Dec;10(12):1101–1121. doi: 10.1016/0022-2828(78)90355-3. [DOI] [PubMed] [Google Scholar]
  8. Isenberg G., Klöckner U. Glycocalyx is not required for show inward calcium current in isolated rat heart myocytes. Nature. 1980 Mar 27;284(5754):358–360. doi: 10.1038/284358a0. [DOI] [PubMed] [Google Scholar]
  9. Kostyuk P. G., Krishtal O. A., Pidoplichko V. I. Calcium inward current and related charge movements in the membrane of snail neurones. J Physiol. 1981 Jan;310:403–421. doi: 10.1113/jphysiol.1981.sp013557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kostyuk P. G., Krishtal O. A., Shakhovalov Y. A. Separation of sodium and calcium currents in the somatic membrane of mollusc neurones. J Physiol. 1977 Sep;270(3):545–568. doi: 10.1113/jphysiol.1977.sp011968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Lee K. S., Akaike N., Brown A. M. Properties of internally perfused, voltage-clamped, isolated nerve cell bodies. J Gen Physiol. 1978 May;71(5):489–507. doi: 10.1085/jgp.71.5.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lee K. S., Tsien R. W. Reversal of current through calcium channels in dialysed single heart cells. Nature. 1982 Jun 10;297(5866):498–501. doi: 10.1038/297498a0. [DOI] [PubMed] [Google Scholar]
  14. Lee K. S., Weeks T. A., Kao R. L., Akaike N., Brown A. M. Sodium current in single heart muscle cells. Nature. 1979 Mar 15;278(5701):269–271. doi: 10.1038/278269a0. [DOI] [PubMed] [Google Scholar]
  15. McDonald T. F., MacLeod D. P. Metabolism and the electrical activity of anoxic ventricular muscle. J Physiol. 1973 Mar;229(3):559–582. doi: 10.1113/jphysiol.1973.sp010154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Meves H. Inactivation of the sodium permeability in squid giant nerve fibres. Prog Biophys Mol Biol. 1978;33(2):207–230. doi: 10.1016/0079-6107(79)90029-4. [DOI] [PubMed] [Google Scholar]
  17. Noble D., Tsien R. W. The kinetics and rectifier properties of the slow potassium current in cardiac Purkinje fibres. J Physiol. 1968 Mar;195(1):185–214. doi: 10.1113/jphysiol.1968.sp008454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Noma A., Kotake H., Irisawa H. Slow inward current and its role mediating the chronotropic effect of epinephrine in the rabbit sinoatrial node. Pflugers Arch. 1980 Oct;388(1):1–9. doi: 10.1007/BF00582621. [DOI] [PubMed] [Google Scholar]
  19. Okamoto H., Takahashi K., Yoshii M. Two components of the calcium current in the egg cell membrane of the tunicate. J Physiol. 1976 Feb;255(2):527–561. doi: 10.1113/jphysiol.1976.sp011294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Powell T., Terrar D. A., Twist V. W. Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol. 1980 May;302:131–153. doi: 10.1113/jphysiol.1980.sp013234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Powell T., Twist V. W. A rapid technique for the isolation and purification of adult cardiac muscle cells having respiratory control and a tolerance to calcium. Biochem Biophys Res Commun. 1976 Sep 7;72(1):327–333. doi: 10.1016/0006-291x(76)90997-9. [DOI] [PubMed] [Google Scholar]
  22. Reuter H. Divalent cations as charge carriers in excitable membranes. Prog Biophys Mol Biol. 1973;26:1–43. doi: 10.1016/0079-6107(73)90016-3. [DOI] [PubMed] [Google Scholar]
  23. Reuter H. Localization of beta adrenergic receptors, and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J Physiol. 1974 Oct;242(2):429–451. doi: 10.1113/jphysiol.1974.sp010716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Reuter H., Scholz H. The regulation of the calcium conductance of cardiac muscle by adrenaline. J Physiol. 1977 Jan;264(1):49–62. doi: 10.1113/jphysiol.1977.sp011657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schneider J. A., Sperelakis N. Slow Ca2+ and Na+ responses induced by isoproterenol and methylxanthines in isolated perfused guinea pig hearts exposed to elevated K+. J Mol Cell Cardiol. 1975 Apr;7(4):249–273. doi: 10.1016/0022-2828(75)90084-x. [DOI] [PubMed] [Google Scholar]
  27. Taniguchi J., Kokubun S., Noma A., Irisawa H. Spontaneously active cells isolated from the sino-atrial and atrio-ventricular nodes of the rabbit heart. Jpn J Physiol. 1981;31(4):547–558. doi: 10.2170/jjphysiol.31.547. [DOI] [PubMed] [Google Scholar]
  28. Trautwein W., Taniguchi J., Noma A. The effect of intracellular cyclic nucleotides and calcium on the action potential and acetylcholine response of isolated cardiac cells. Pflugers Arch. 1982 Feb;392(4):307–314. doi: 10.1007/BF00581624. [DOI] [PubMed] [Google Scholar]
  29. Tsien R. W. Adrenaline-like effects of intracellular iontophoresis of cyclic AMP in cardiac Purkinje fibres. Nat New Biol. 1973 Sep 26;245(143):120–122. doi: 10.1038/newbio245120a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES