Sustained subthreshold-for-twitch depolarization in rat single ventricular myocytes causes sustained calcium channel activation and sarcoplasmic reticulum calcium release

Antti Talo, Michael D. Stern, Harold A. Spurgeon, Gerrit Isenberg, Edward G. Lakatra

Research output: Contribution to journalArticlepeer-review

Abstract

Single rat ventricular myocytes, voltage-clamped at -50 to -40 mV, were depolarized in small steps in order to define the mechanisms that govern the increase in cytosolic [Ca2+] (Cai) and contraction, measured as a reduction in myocyte length. Small (3-5 mV), sustained (seconds) depolarizations that caused a small inward or no detectable change in current were followed after a delay by small (<2% of the resting length), steady reductions in cell length measured via a photodiode array, and small, steady increases in Cai measured by changes in Indo-1 fluorescence. Larger (greater than - 30 and less than - 20 mV), sustained depolarizations produced phasic Ca2+ currents, Cai transients, and twitch contractions, followed by a steady current and a steady increase in Cai and contraction. Nitrendipine (or Cd, verapamil, or Ni) abolished the steady contraction and always produced an outward shift in steady current. The steady, nitrendipine-sensitive current and sustained increase in Cai and contraction exhibited a similar voltage dependence over the voltage range between - 40 and -20 mV. 2 µM ryanodine in the presence of intact Ca2+ channel activity also abolished the steady increase in Cai and contraction over this voltage range. We conclude that when a sustained depolarization does not exceed about -20 mV, the resultant steady, graded contraction is due to SR Ca2+ release graded by a steady ("window") Ca2+ current. The existence of appreciable, sustained, graded Ca2+ release in response to Ca2+ current generated by arbitrarily small depolarizations is not compatible with any model of Ca2+-induced Ca2+ release in which the releasing effect of the Ca2+ channel current is mediated solely by Ca2+ entry into a common cytosolic pool. Our results therefore imply a distinction between the triggering and released Ca2+ pools.

Original languageEnglish (US)
Pages (from-to)1085-1103
Number of pages19
JournalJournal of General Physiology
Volume96
Issue number5
DOIs
StatePublished - Nov 1 1990

ASJC Scopus subject areas

  • Physiology

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