Effects of sarcoplasmic reticulum Ca2+ load on the gain function of Ca2+ release by Ca2+ current in cardiac cells

A. M. Janczewski, H. A. Spurgeon, M. D. Stern, E. G. Lakatta

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We studied the effects of variable sarcoplasmic reticulum (SR) Ca2+ leading on changes in the gain index of Ca2+ release from the SR, measured as the ratio of the amount of Ca2+ released to the magnitude of the Ca2+ current (I(Ca)) integrated for the initial 20 ms of the depolarization, in whole cell voltage-clamped rat ventricular myocytes dialyzed with the Ca2+ indicator indo 1 salt at 23°C. Changes in I(Ca) were measured directly, and changes in the SR Ca2+ release were indexed by changes in the amplitudes and rates of rise of cytosolic Ca2+ (Ca(i)/2+) transients. The SR Ca2+ lead was graded by the duration of conditioning voltage-clamp steps and verified by caffeine-dependent Ca(i)/2+ transients. A train of abbreviated (from 100 to 20 ms) voltage-clamp depolarizations, which triggers SR Ca2+ release but falls to replenish the SR with Ca2+, diminished the SR Ca2+ lead by 56 ± 5%, did not alter peak I(Ca) but reduced the amplitudes of the I(Ca)-dependent Ca(i)/2+ transients by 52 ± 3%, and decreased the gain index by 60 ± 3% (SE; n = 5 or 6). Changes in the amplitudes of Ca(i)/2+ transients elicited by I(Ca) and changes in the gain index were linearly correlated (r2 = 0.83 and 0.79, respectively; P < 0.001 for each) with changes in amplitudes of Ca(i)/2+ transients elicited by caffeine pulses applied in lieu of the respective voltage-clamp pulses. The linear dependence of gain on SR Ca2+ loading provides further evidence against the existence of strong positive feedback of released Ca2+ on the Ca2+ release triggering mechanism and has theoretical implications for force-interval and staircase phenomena in the heart.

Original languageEnglish (US)
Pages (from-to)H916-H920
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2 37-2
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

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


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