Citrate alters Ca channel gating and selectivity in rabbit ventricular myocytes

L. V. Hryshko, Donald M Bers

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Addition of 10 mM citrate at constant free extracellular Ca concentration ([Ca](o); 2 mM) reduced contraction in rabbit ventricular muscle and isolated myocytes. We have recently shown that extracellular citrate decreases contraction and Ca current (I(Ca)) in cardiac muscle by a direct effect on Ca channels rather than by Ca buffering per se [D. M. Bers, L. V. Hryshko, S. M. Harrison, and D. Dawson. Am. J. Physiol. 260 (Cell Physiol. 29): C900-C909, 1991]. Citrate rapidly depressed peak I(Ca) and shifted both the peak I(Ca) and the apparent reversal potential (E(rev)) to more negative potentials. When the impermeant cations, tetraethylammonium or N-methylglucamine were used instead of intracellular Cs, the citrate-induced shift in E(rev) was reduced or eliminated but depression of I(Ca) was still observed. Thus citrate appears to alter the selectivity (P(Ca)/P(Cs)) of the Ca channel and reduce I(Ca). We also studied the effects of citrate on Na current through the Ca channel, observed when the divalent cation concentration is submicromolar. This current, termed I(NS) for nonspecific, also exhibited leftward shifts in peak I(NS) and smaller changes in E(rev) in the presence of citrate. However, neither peak I(NS) nor single-channel conductance were affected by citrate. Thus the reduced P(Ca)/P(Ca) is due primarily to alteration of Ca permeation rather than monovalent cation permeation. Activation and inactivation curves for both I(Ca) and I(NS) were shifted toward more negative potentials by citrate. The shifts in gating and peak current to more negative membrane potentials would be consistent with a surface charge effect. The much larger shift in E(rev) for I(Ca) (than for I(NS)) is consistent with a reduction in Ca selectivity. We conclude that citrate alters I(Ca) by a combination of gating shifts (which may result from changes in surface potential) and altered Ca channel selectivity (which may result from altered Ca permeation).

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume262
Issue number1 31-1
StatePublished - 1992

Keywords

  • Calcium current
  • Membrane potential
  • Nonspecific current
  • Reversal potential
  • Surface charge

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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