Inactivation of calcium channels in mammalian heart cells: joint dependence on membrane potential and intracellular calcium.

K. S. Lee, E. Marban, R. W. Tsien

Research output: Contribution to journalArticle

Abstract

Ca channel currents were recorded in Cs‐loaded calf cardiac Purkinje fibres and Cs‐dialysed myocytes from guinea‐pig ventricle to evaluate the dependence of Ca channel inactivation on membrane depolarization and intracellular free Ca concentration ([Ca]i). The decay of Ca channel current during a maintained depolarization was slowed when external Ca was replaced by Sr or Ba. The decay reflected a genuine inactivation of Ca channel conductance, as assessed by the decreased amplitude of inward tail currents following progressively longer depolarizing pulses in ventricular cells. Increasing depolarization slowed inward current inactivation in the presence of extracellular Ca concentration ([Ca]o), but speeded inactivation in the presence of extracellular Ba concentration ([Ba]o), suggesting the participation of fundamentally different mechanisms. Ca channel currents were recorded in Ca‐free external solutions to study 'voltage‐dependent inactivation'. Inactivation of outward Ca channel current due to Cs efflux was seen with external Ba or in the absence of any permeant divalent cation. With Ca as the charge carrier, increasing [Ca]o speeded the rate of inactivation as expected for [Ca]i‐dependent inactivation. The relationship between inactivation and the intracellular Ca transient was assessed by double‐pulse experiments. Conditioning pulses that produced maximal inward Ca current and contractile tension left behind more inactivation than either stronger or weaker depolarizations. The agreement between maximal inward current and maximal inactivation remained close when their voltage dependence was shifted along the voltage axis by elevation of [Ca]o. We conclude that inactivation of cardiac Ca channels is both [Ca]i dependent and voltage dependent. The [Ca]i‐dependent process may serve as a negative feed‐back mechanism for regulating Ca entry into heart cells; the voltage‐dependent mechanism may prevent a secondary rise in Ca channel current when intracellular Ca falls during maintained depolarization of cardiac cells.

Original languageEnglish (US)
Pages (from-to)395-411
Number of pages17
JournalJournal of Physiology
Volume364
Issue number1
DOIs
StatePublished - Jul 1 1985
Externally publishedYes

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Calcium Channels
Membrane Potentials
Joints
Calcium
Purkinje Fibers
Intracellular Membranes
Divalent Cations
Muscle Cells

ASJC Scopus subject areas

  • Physiology

Cite this

Inactivation of calcium channels in mammalian heart cells : joint dependence on membrane potential and intracellular calcium. / Lee, K. S.; Marban, E.; Tsien, R. W.

In: Journal of Physiology, Vol. 364, No. 1, 01.07.1985, p. 395-411.

Research output: Contribution to journalArticle

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