Mechanisms of inactivation of L-type calcium channels in human atrial myocytes

Hui Sun, Normand Leblanc, Stanley Nattel

Research output: Contribution to journalArticlepeer-review

Abstract

We used whole cell patch-clamp and microfluorimetric (indo 1) techniques to measure Ca2+ current through L-type Ca2+ channels (I(Ca)) and Ca2+ transients in human atrial myocytes. During 1-s depolarizing pulses, I(Ca) inactivation was biexponential. The rate of rapid inactivation was slowed by ryanodine and was correlated with the rate of rise of cytoplasmic free Ca2+ concentration (r = 0.80, P < 0.01). Slower-phase I(Ca) inactivation was not affected by ryanodine but was accelerated by increasing the availability of Ca2+ to permeate the Ca2+ channel. Thus Ca2+ released from the sarcoplasmic reticulum (SR) was responsible for most I(Ca) inactivation during the first 50 ms of a depolarization to 0 mV, and thereafter inactivation by Ca2+ permeating the channel predominated. Pure voltage- dependent inactivation had a much slower time course of development (τ > 2s) and played a smaller role than Ca2+-dependent mechanisms over a duration comparable to that of an action potential. We conclude that human atrial myocytes show both voltage- and Ca2+-dependent I(Ca) inactivation, that Ca2+-dependent mechanisms predominate over the time course of an action potential, and that although both Ca2+ released from the SR and Ca2+ permeating Ca2+ channels play a role, SR-released Ca2+ is particularly important in early, rapid I(Ca) inactivation, whereas Ca2+ permeating Ca2+ channels is more important in the slower phase of Ca2+-dependent inactivation.

Original languageEnglish (US)
Pages (from-to)H1625-H1635
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume272
Issue number4 41-4
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Keywords

  • patch clamp
  • permeating calcium ion

ASJC Scopus subject areas

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

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