Abstract
In low K+ (0.3 mM) solutions rabbit sinus node preparations show the oscillatory transient inward current, iTI, already recorded in these conditions in Purkinje and ventricular preparations. The time course of iTI closely resembles that of the slow component of the slow inward current (isi) previously reported by us (Brown, Kimura, Noble, Noble & Taupignon, 1984a) in rabbit sinus node, when recorded near its threshold (-40 mV). When the duration of voltage-clamp steps is varied there is a strong correlation between the 'envelope' of isi amplitudes on depolarization and the time course of iTI on hyperpolarization. Although oscillations of iTI become smaller near 0 mV, there is no potential at which the current records are completely flat, suggesting that there is no simple reversal potential. 75% substitution of Na+ by Li+ greatly reduces both iTI and slow isi in about the same proportion. Reducing the activity of the Na-K exchange pump by the amount expected in 0.3 mM-K+ solutions is sufficient to induce oscillatory iTI in a computer model of the sino-atrial node (Noble & Noble, 1984). The model reproduces the current as variations in the Na-Ca exchange current dependent on intracellular Ca2+ concentration ([ Ca]i). The model was also used to test the alternative hypothesis that the slow inward currents might be generated by [Ca]i-activated non-specific cation channels. It is shown that this would distort the shape of the repolarization phase of the action potential. It is concluded that the experiments and computations are consistent with the hypothesis that a large fraction of iTI and the slow component of isi could both be generated by Na-Ca exchange and that only a relatively small fraction might be generated by non-specific channels.
Full text
PDF
















Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allen D. G., Eisner D. A., Orchard C. H. Characterization of oscillations of intracellular calcium concentration in ferret ventricular muscle. J Physiol. 1984 Jul;352:113–128. doi: 10.1113/jphysiol.1984.sp015281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arlock P., Katzung B. G. Effects of sodium substitutes on transient inward current and tension in guinea-pig and ferret papillary muscle. J Physiol. 1985 Mar;360:105–120. doi: 10.1113/jphysiol.1985.sp015606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown H. F., Kimura J., Noble D., Noble S. J., Taupignon A. The ionic currents underlying pacemaker activity in rabbit sino-atrial node: experimental results and computer simulations. Proc R Soc Lond B Biol Sci. 1984 Sep 22;222(1228):329–347. doi: 10.1098/rspb.1984.0067. [DOI] [PubMed] [Google Scholar]
- Brown H. F., Kimura J., Noble D., Noble S. J., Taupignon A. The slow inward current, isi, in the rabbit sino-atrial node investigated by voltage clamp and computer simulation. Proc R Soc Lond B Biol Sci. 1984 Sep 22;222(1228):305–328. doi: 10.1098/rspb.1984.0066. [DOI] [PubMed] [Google Scholar]
- Brown H., Difrancesco D. Voltage-clamp investigations of membrane currents underlying pace-maker activity in rabbit sino-atrial node. J Physiol. 1980 Nov;308:331–351. doi: 10.1113/jphysiol.1980.sp013474. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- DiFrancesco D., Noble D. A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Philos Trans R Soc Lond B Biol Sci. 1985 Jan 10;307(1133):353–398. doi: 10.1098/rstb.1985.0001. [DOI] [PubMed] [Google Scholar]
- Eisner D. A., Lederer W. J. Inotropic and arrhythmogenic effects of potassium-depleted solutions on mammalian cardiac muscle. J Physiol. 1979 Sep;294:255–277. doi: 10.1113/jphysiol.1979.sp012929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FATT P., KATZ B. An analysis of the end-plate potential recorded with an intracellular electrode. J Physiol. 1951 Nov 28;115(3):320–370. doi: 10.1113/jphysiol.1951.sp004675. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol. 1983 Jul;245(1):C1–14. doi: 10.1152/ajpcell.1983.245.1.C1. [DOI] [PubMed] [Google Scholar]
- Fabiato A., Fabiato F. Contractions induced by a calcium-triggered release of calcium from the sarcoplasmic reticulum of single skinned cardiac cells. J Physiol. 1975 Aug;249(3):469–495. doi: 10.1113/jphysiol.1975.sp011026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greene R. W., Haas H. L. Adenosine actions on CA1 pyramidal neurones in rat hippocampal slices. J Physiol. 1985 Sep;366:119–127. doi: 10.1113/jphysiol.1985.sp015788. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hilton S. M., Marshall J. M., Timms R. J. Ventral medullary relay neurones in the pathway from the defence areas of the cat and their effect on blood pressure. J Physiol. 1983 Dec;345:149–166. doi: 10.1113/jphysiol.1983.sp014971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karagueuzian H. S., Katzung B. G. Voltage-clamp studies of transient inward current and mechanical oscillations induced by ouabain in ferret papillary muscle. J Physiol. 1982 Jun;327:255–271. doi: 10.1113/jphysiol.1982.sp014230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kass R. S., Lederer W. J., Tsien R. W., Weingart R. Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978 Aug;281:187–208. doi: 10.1113/jphysiol.1978.sp012416. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lederer W. J., Tsien R. W. Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J Physiol. 1976 Dec;263(2):73–100. doi: 10.1113/jphysiol.1976.sp011622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noble D., Noble S. J. A model of sino-atrial node electrical activity based on a modification of the DiFrancesco-Noble (1984) equations. Proc R Soc Lond B Biol Sci. 1984 Sep 22;222(1228):295–304. doi: 10.1098/rspb.1984.0065. [DOI] [PubMed] [Google Scholar]
- Noble D. The surprising heart: a review of recent progress in cardiac electrophysiology. J Physiol. 1984 Aug;353:1–50. doi: 10.1113/jphysiol.1984.sp015320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noma A., Irisawa H. Membrane currents in the rabbit sinoatrial node cell as studied by the double microelectrode method. Pflugers Arch. 1976 Jun 29;364(1):45–52. doi: 10.1007/BF01062910. [DOI] [PubMed] [Google Scholar]
- Yellen G. Single Ca2+-activated nonselective cation channels in neuroblastoma. Nature. 1982 Mar 25;296(5855):357–359. doi: 10.1038/296357a0. [DOI] [PubMed] [Google Scholar]