Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1988 Sep;403:239–266. doi: 10.1113/jphysiol.1988.sp017248

Ion transfer characteristics of the calcium current in bull-frog atrial myocytes.

D L Campbell 1, W R Giles 1, E F Shibata 1
PMCID: PMC1190712  PMID: 2855341

Abstract

1. Voltage clamp studies on single cells from bull-frog atrium have been carried out to study the ion transfer characteristics of the calcium current, ICa. In agreement with the preliminary results of Hume & Giles (1983), a TTX-resistant, 'second transient inward current' was recorded consistently. Its average peak size at 0 mV in 2.5 mM [Ca2+]o Ringer solution was approximately -200 pA, and it was blocked by Cd2+ and La3+ but not by tetrodotoxin (TTX, 3 x 10(-6) M). 2. The peak size of this current increases by approximately 4 times when [Ca2+]o is raised from 1.25 to 7.5 mM, indicating that Ca2+ is a major charge carrier. 3. A well-defined reversal potential, Erev, for ICa can be recorded in normal Ringer solution and also when Ba2+ or Sr2+ serve as the charge carriers. When [Ca2+]o is changed the shifts in Erev follow the predictions of a Nernstian Ca2+ electrode. However, all Erev values are well below those predicted from the thermodynamic Nernstian ECa values (see Campbell, Giles, Hume, Noble & Shibata, 1988a). 4. The Ca2+ current exhibits voltage-dependent inactivation, whether the direction of net current flow is inward or outward; however, the rate of inactivation is affected by the species of cation carrying the current. Inactivation is reduced substantially in Ba2+ Ringer solution. 5. Magnesium (5 mM) is not a significant carrier or blocker of ICa in normal [Ca2+]o Ringer solution; however, 5 mM [Mg2+]o can block the current carried by either Sr2+ or Ba2+. In the absence of Mg2+, equimolar substitutions of Sr2+ or Ba2+ for Ca2+ result in larger currents than those carried by Ca2+ in the normal Ringer solution. 6. Sodium appears not to be a significant charge carrier in the presence of normal [Ca2+]o. However, after free [Ca2+]o has been reduced to extremely low levels (less than 10(-6) M) Na+ can carry a significant fraction of 'ICa'. Thus, it appears that the high selectivity of ICa for Ca2+ ions depends upon the presence of Ca2+. 7. 'Slow tails' are frequently recorded after repolarizing clamp steps back to the holding potential. These 'slow tails' are prominent in normal [Na+]o, [Ca2+]o and [Sr2+]o Ringer solution; however, they are markedly reduced in [Ba2+]o, in Na+-free and Ca2+-free Ringer solutions. Experimental and theoretical work suggests these slow tails may be generated by an electrogenic Na+-Ca2+ exchanger (see Campbell, Giles, Robinson & Shibata, 1988b).(ABSTRACT TRUNCATED AT 400 WORDS)

Full text

PDF
239

Selected References

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

  1. Akaike N., Lee K. S., Brown A. M. The calcium current of Helix neuron. J Gen Physiol. 1978 May;71(5):509–531. doi: 10.1085/jgp.71.5.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Almers W., McCleskey E. W. Non-selective conductance in calcium channels of frog muscle: calcium selectivity in a single-file pore. J Physiol. 1984 Aug;353:585–608. doi: 10.1113/jphysiol.1984.sp015352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Almers W., McCleskey E. W., Palade P. T. A non-selective cation conductance in frog muscle membrane blocked by micromolar external calcium ions. J Physiol. 1984 Aug;353:565–583. doi: 10.1113/jphysiol.1984.sp015351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Attwell D., Cohen I. The voltage clamp of multicellular preparations. Prog Biophys Mol Biol. 1977;31(3):201–245. doi: 10.1016/0079-6107(78)90009-3. [DOI] [PubMed] [Google Scholar]
  5. Bonvallet R. A low threshold calcium current recorded at physiological Ca concentrations in single frog atrial cells. Pflugers Arch. 1987 May;408(5):540–542. doi: 10.1007/BF00585084. [DOI] [PubMed] [Google Scholar]
  6. Byerly L., Chase P. B., Stimers J. R. Permeation and interaction of divalent cations in calcium channels of snail neurons. J Gen Physiol. 1985 Apr;85(4):491–518. doi: 10.1085/jgp.85.4.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Campbell D. L., Giles W. R., Hume J. R., Noble D., Shibata E. F. Reversal potential of the calcium current in bull-frog atrial myocytes. J Physiol. 1988 Sep;403:267–286. doi: 10.1113/jphysiol.1988.sp017249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Campbell D. L., Giles W. R., Robinson K., Shibata E. F. Studies of the sodium-calcium exchanger in bull-frog atrial myocytes. J Physiol. 1988 Sep;403:317–340. doi: 10.1113/jphysiol.1988.sp017251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cavalié A., McDonald T. F., Pelzer D., Trautwein W. Temperature-induced transitory and steady-state changes in the calcium current of guinea pig ventricular myocytes. Pflugers Arch. 1985 Oct;405(3):294–296. doi: 10.1007/BF00582574. [DOI] [PubMed] [Google Scholar]
  11. Chapman R. A. Excitation-contraction coupling in cardiac muscle. Prog Biophys Mol Biol. 1979;35(1):1–52. doi: 10.1016/0079-6107(80)90002-4. [DOI] [PubMed] [Google Scholar]
  12. Clark R. B., Giles W. Sodium current in single cells from bullfrog atrium: voltage dependence and ion transfer properties. J Physiol. 1987 Oct;391:235–265. doi: 10.1113/jphysiol.1987.sp016736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Colquhoun D., Neher E., Reuter H., Stevens C. F. Inward current channels activated by intracellular Ca in cultured cardiac cells. Nature. 1981 Dec 24;294(5843):752–754. doi: 10.1038/294752a0. [DOI] [PubMed] [Google Scholar]
  14. Connor J., Barr L., Jakobsson E. Electrical characteristics of frog atrial trabeculae in the double sucrose gap. Biophys J. 1975 Oct;15(10):1047–1067. doi: 10.1016/S0006-3495(75)85882-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Durham A. C. A survey of readily available chelators for buffering calcium ion concentrations in physiological solutions. Cell Calcium. 1983 Feb;4(1):33–46. doi: 10.1016/0143-4160(83)90047-7. [DOI] [PubMed] [Google Scholar]
  16. FRANKENHAEUSER B., HODGKIN A. L. The action of calcium on the electrical properties of squid axons. J Physiol. 1957 Jul 11;137(2):218–244. doi: 10.1113/jphysiol.1957.sp005808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fukushima Y., Hagiwara S. Currents carried by monovalent cations through calcium channels in mouse neoplastic B lymphocytes. J Physiol. 1985 Jan;358:255–284. doi: 10.1113/jphysiol.1985.sp015550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Giles W. R., Shibata E. F. Voltage clamp of bull-frog cardiac pace-maker cells: a quantitative analysis of potassium currents. J Physiol. 1985 Nov;368:265–292. doi: 10.1113/jphysiol.1985.sp015857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hagiwara S., Byerly L. Calcium channel. Annu Rev Neurosci. 1981;4:69–125. doi: 10.1146/annurev.ne.04.030181.000441. [DOI] [PubMed] [Google Scholar]
  20. Hagiwara S., Jaffe L. A. Electrical properties of egg cell membranes. Annu Rev Biophys Bioeng. 1979;8:385–416. doi: 10.1146/annurev.bb.08.060179.002125. [DOI] [PubMed] [Google Scholar]
  21. Hagiwara S., Nakajima S. Tetrodotoxin and manganese ion: effects on action potential of the frog heart. Science. 1965 Sep 10;149(3689):1254–1255. doi: 10.1126/science.149.3689.1254. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Hess P., Tsien R. W. Mechanism of ion permeation through calcium channels. 1984 May 31-Jun 6Nature. 309(5967):453–456. doi: 10.1038/309453a0. [DOI] [PubMed] [Google Scholar]
  25. Hille B. Charges and potentials at the nerve surface. Divalent ions and pH. J Gen Physiol. 1968 Feb;51(2):221–236. doi: 10.1085/jgp.51.2.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hille B., Schwarz W. Potassium channels as multi-ion single-file pores. J Gen Physiol. 1978 Oct;72(4):409–442. doi: 10.1085/jgp.72.4.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Horackova M., Vassort G. Sodium-calcium exchange in regulation of cardiac contractility. Evidence for an electrogenic, voltage-dependent mechanism. J Gen Physiol. 1979 Apr;73(4):403–424. doi: 10.1085/jgp.73.4.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hume J. R. Component of whole cell Ca current due to electrogenic Na-Ca-exchange in cardiac myocytes. Am J Physiol. 1987 Mar;252(3 Pt 2):H666–H670. doi: 10.1152/ajpheart.1987.252.3.H666. [DOI] [PubMed] [Google Scholar]
  29. Hume J. R., Giles W. Ionic currents in single isolated bullfrog atrial cells. J Gen Physiol. 1983 Feb;81(2):153–194. doi: 10.1085/jgp.81.2.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hume J. R., Giles W., Robinson K., Shibata E. F., Nathan R. D., Kanai K., Rasmusson R. A time- and voltage-dependent K+ current in single cardiac cells from bullfrog atrium. J Gen Physiol. 1986 Dec;88(6):777–798. doi: 10.1085/jgp.88.6.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Hume J. R., Uehara A. "Creep currents" in single frog atrial cells may be generated by electrogenic Na/Ca exchange. J Gen Physiol. 1986 Jun;87(6):857–884. doi: 10.1085/jgp.87.6.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Isenberg G., Klöckner U. Calcium currents of isolated bovine ventricular myocytes are fast and of large amplitude. Pflugers Arch. 1982 Oct;395(1):30–41. doi: 10.1007/BF00584965. [DOI] [PubMed] [Google Scholar]
  33. Johnson E. A., Lieberman M. Heart: excitation and contraction. Annu Rev Physiol. 1971;33:479–532. doi: 10.1146/annurev.ph.33.030171.002403. [DOI] [PubMed] [Google Scholar]
  34. Josephson I. R., Sanchez-Chapula J., Brown A. M. A comparison of calcium currents in rat and guinea pig single ventricular cells. Circ Res. 1984 Feb;54(2):144–156. doi: 10.1161/01.res.54.2.144. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Kass R. S., Siegelbaum S. A., Tsien R. W. Three-micro-electrode voltage clamp experiments in calf cardiac Purkinje fibres: is slow inward current adequately measured? J Physiol. 1979 May;290(2):201–225. doi: 10.1113/jphysiol.1979.sp012768. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kostyuk P. G. Calcium channels in the neuronal membrane. Biochim Biophys Acta. 1981 Dec;650(2-3):128–150. doi: 10.1016/0304-4157(81)90003-4. [DOI] [PubMed] [Google Scholar]
  38. Kostyuk P. G. Calcium ionic channels in electrically excitable membrane. Neuroscience. 1980;5(6):945–959. doi: 10.1016/0306-4522(80)90178-5. [DOI] [PubMed] [Google Scholar]
  39. Kostyuk P. G., Krishtal O. A. Effects of calcium and calcium-chelating agents on the inward and outward current in the membrane of mollusc neurones. J Physiol. 1977 Sep;270(3):569–580. doi: 10.1113/jphysiol.1977.sp011969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lammel E. A theoretical study on the sucrose gap technique as applied to multicellular muscle preparations. I. Saline-sucrose interdiffusion. Biophys J. 1981 Dec;36(3):533–553. doi: 10.1016/S0006-3495(81)84751-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lansman J. B., Hess P., Tsien R. W. Blockade of current through single calcium channels by Cd2+, Mg2+, and Ca2+. Voltage and concentration dependence of calcium entry into the pore. J Gen Physiol. 1986 Sep;88(3):321–347. doi: 10.1085/jgp.88.3.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lee K. S., Tsien R. W. High selectivity of calcium channels in single dialysed heart cells of the guinea-pig. J Physiol. 1984 Sep;354:253–272. doi: 10.1113/jphysiol.1984.sp015374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Levi R., DeFelice L. J. Sodium-conducting channels in cardiac membranes in low calcium. Biophys J. 1986 Jul;50(1):5–9. doi: 10.1016/S0006-3495(86)83433-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. McDonald T. F., Cavalié A., Trautwein W., Pelzer D. Voltage-dependent properties of macroscopic and elementary calcium channel currents in guinea pig ventricular myocytes. Pflugers Arch. 1986 May;406(5):437–448. doi: 10.1007/BF00583365. [DOI] [PubMed] [Google Scholar]
  47. 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]
  48. Mentrard D., Vassort G., Fischmeister R. Calcium-mediated inactivation of the calcium conductance in cesium-loaded frog heart cells. J Gen Physiol. 1984 Jan;83(1):105–131. doi: 10.1085/jgp.83.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Mentrard D., Vassort G., Fischmeister R. Changes in external Na induce a membrane current related to the Na-Ca exchange in cesium-loaded frog heart cells. J Gen Physiol. 1984 Aug;84(2):201–220. doi: 10.1085/jgp.84.2.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Mitchell M. R., Powell T., Terrar D. A., Twist V. W. Characteristics of the second inward current in cells isolated from rat ventricular muscle. Proc R Soc Lond B Biol Sci. 1983 Oct 22;219(1217):447–469. doi: 10.1098/rspb.1983.0084. [DOI] [PubMed] [Google Scholar]
  51. Moisescu D. G. Kinetics of reaction in calcium-activated skinned muscle fibres. Nature. 1976 Aug 12;262(5569):610–613. doi: 10.1038/262610a0. [DOI] [PubMed] [Google Scholar]
  52. Morad M., Goldman Y. E., Trentham D. R. Rapid photochemical inactivation of Ca2+-antagonists shows that Ca2+ entry directly activates contraction in frog heart. Nature. 1983 Aug 18;304(5927):635–638. doi: 10.1038/304635a0. [DOI] [PubMed] [Google Scholar]
  53. Muller R. U., Finkelstein A. The electrostatic basis of Mg++ inhibition of transmitter release. Proc Natl Acad Sci U S A. 1974 Mar;71(3):923–926. doi: 10.1073/pnas.71.3.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Mullins L. J. The generation of electric currents in cardiac fibers by Na/Ca exchange. Am J Physiol. 1979 Mar;236(3):C103–C110. doi: 10.1152/ajpcell.1979.236.3.C103. [DOI] [PubMed] [Google Scholar]
  55. Nelson M. T. Interactions of divalent cations with single calcium channels from rat brain synaptosomes. J Gen Physiol. 1986 Feb;87(2):201–222. doi: 10.1085/jgp.87.2.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Niedergerke R., Orkand R. K. The dual effect of calcium on the action potential of the frog's heart. J Physiol. 1966 May;184(2):291–311. doi: 10.1113/jphysiol.1966.sp007916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Page S. G., Niedergerke R. Structures of physiological interest in the frog heart ventricle. J Cell Sci. 1972 Jul;11(1):179–203. doi: 10.1242/jcs.11.1.179. [DOI] [PubMed] [Google Scholar]
  58. Provencher S. W. A Fourier method for the analysis of exponential decay curves. Biophys J. 1976 Jan;16(1):27–41. doi: 10.1016/S0006-3495(76)85660-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. 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]
  60. 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]
  61. Robertson S. P., Johnson J. D., Potter J. D. The time-course of Ca2+ exchange with calmodulin, troponin, parvalbumin, and myosin in response to transient increases in Ca2+. Biophys J. 1981 Jun;34(3):559–569. doi: 10.1016/S0006-3495(81)84868-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Robinson K., Giles W. A data acquisition, display and plotting program for the IBM PC. Comput Methods Programs Biomed. 1986 Dec;23(3):319–327. doi: 10.1016/0169-2607(86)90067-2. [DOI] [PubMed] [Google Scholar]
  63. Rougier O., Vassort G., Garnier D., Gargouil Y. M., Coraboeuf E. Existence and role of a slow inward current during the frog atrial action potential. Pflugers Arch. 1969;308(2):91–110. doi: 10.1007/BF00587018. [DOI] [PubMed] [Google Scholar]
  64. Rougier O., Vassort G., Stämpfli R. Voltage clamp experiments on frog atrial heart muscle fibres with the sucrose gap technique. Pflugers Arch Gesamte Physiol Menschen Tiere. 1968;301(2):91–108. doi: 10.1007/BF00362729. [DOI] [PubMed] [Google Scholar]
  65. Tarr M., Trank J. Equivalent circuit of frog atrial tissue as determined by voltage clamp-unclamp experiments. J Gen Physiol. 1971 Nov;58(5):511–522. doi: 10.1085/jgp.58.5.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Tarr M. Two inward currents in frog atrial muscle. J Gen Physiol. 1971 Nov;58(5):523–543. doi: 10.1085/jgp.58.5.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Tsien R. W., Bean B. P., Hess P., Nowycky M. Calcium channels: mechanisms of beta-adrenergic modulation and ion permeation. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 1):201–212. doi: 10.1101/sqb.1983.048.01.023. [DOI] [PubMed] [Google Scholar]
  68. Tsien R. W. Calcium channels in excitable cell membranes. Annu Rev Physiol. 1983;45:341–358. doi: 10.1146/annurev.ph.45.030183.002013. [DOI] [PubMed] [Google Scholar]
  69. Tung L., Morad M. A comparative electrophysiological study of enzymatically isolated single cells and strips of frog ventricle. Pflugers Arch. 1985 Oct;405(3):274–284. doi: 10.1007/BF00582572. [DOI] [PubMed] [Google Scholar]
  70. Vassort G., Rougier O., Garnier D., Sauviat M. P., Coraboeuf E., Gargouïl Y. M. Effects of adrenaline on membrane inward currents during the cardiac action potential. Pflugers Arch. 1969;309(1):70–81. doi: 10.1007/BF00592283. [DOI] [PubMed] [Google Scholar]
  71. WRIGHT E. B., OGATA M. Action potential of amphibian single auricular muscle fiber: a dual response. Am J Physiol. 1961 Dec;201:1101–1108. doi: 10.1152/ajplegacy.1961.201.6.1101. [DOI] [PubMed] [Google Scholar]
  72. Wilson D. L., Morimoto K., Tsuda Y., Brown A. M. Interaction between calcium ions and surface charge as it relates to calcium currents. J Membr Biol. 1983;72(1-2):117–130. doi: 10.1007/BF01870319. [DOI] [PubMed] [Google Scholar]
  73. Yamamoto D., Washio H. Permeation of sodium through calcium channels of an insect muscle membrane. Can J Physiol Pharmacol. 1979 Feb;57(2):220–222. doi: 10.1139/y79-033. [DOI] [PubMed] [Google Scholar]
  74. de Hemptinne A. Voltage clamp analysis in isolated cardiac fibres as performed with two different perfusion chambres for double sucrose gap. Pflugers Arch. 1976 May 6;363(1):87–95. doi: 10.1007/BF00587407. [DOI] [PubMed] [Google Scholar]

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

RESOURCES