Ca2+-activated Cl- current can be triggered by Na+ current-induced SR Ca2+ release in rabbit ventricle

Hui Sun, Denis Chartier, Stanley Nattel, Normand Leblanc

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


The Ca2+-activated Cl- current [I(Cl(Ca))] contributes to the repolarization of the cardiac action potential under physiological conditions. I(Cl(Ca)) is known to be primarily activated by Ca2+ release from the sarcoplasmic reticulum (SR). L-type Ca2+ current [I(Ca(L))] represents the major trigger for Ca2+ release in the heart. Recent evidence, however, suggests that Ca2+ entry via reverse-mode Na+/Ca2+ exchange promoted by voltage and/or Na+ current (I(Na)) may also play a role. The purpose of this study was to test the hypothesis that I(Cl(Ca)) can be induced by I(Na) in the absence of I(Ca(L)). Macroscopic currents and Ca2+ transients were measured using the whole cell patch-clamp technique in rabbit ventricular myocytes loaded with Indo-1. Nicardipine (10 μM) abolished I(Ca(L)) at a holding potential of -75 mV as tested in Na+-free external solution. In the presence of 131 mM external Na+ and in the absence of I(Ca(L)), a 4-aminopyridine-resistant transient outward current was recorded in 64 of 81 cells accompanying a phasic Ca2+ transient. The current reversed at -42.0 ± 1.3 mV (n = 6) and at +0.3 ± 1.4 mV (n = 6) with 21 and 141 mM of internal Cl-, respectively, similar to the predicted reversal potential with low intracellular Cl- concentration ([Cl-](i)) (- 47.8 mV) and high [Cl-](i) (-1.2 mV). Niflumic acid (100 μM) inhibited the current without affecting the Ca2+ signal (n = 8). Both the current and Ca2+ transient were abolished by 10 mM caffeine (n = 6), 10 μM ryanodine (n = 3), 30 μM tetrodotoxin (n = 9), or removal of extracellular Ca2+ (n = 6). These properties are consistent with those of I(Cl(Ca)) previously described in mammalian cardiac myocytes. We conclude that 1) I(Cl(Ca)) can be recorded in the absence of I(Ca(L)), and 2) I(Na)-induced SR Ca2+ release mechanism is also present in the rabbit heart and may play a physiological role in activating the Ca2+-sensitive membrane Cl- conductance.

Original languageEnglish (US)
Pages (from-to)H1467-H1477
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4 46-4
StatePublished - Oct 1999
Externally publishedYes


  • Chloride ion channel
  • Electrophysiology
  • Excitation-contraction coupling
  • Heart
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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