Variability of Spontaneous Ca2+ Release Between Different Rat Ventricular Myocytes Is Correlated with Na+-Ca2+ Exchange and [Na+]i

M. E. Díaz, S. J. Cook, J. P. Chamunorwa, A. W. Trafford, M. K. Lancaster, Stephen O'Neill, David Eisner

    Research output: Contribution to journalArticlepeer-review

    Abstract

    We have studied the factors responsible for the variation of the frequency of "waves" caused by spontaneous Ca2+ release in rat ventricular myocytes. The experiments were performed in isolated myocytes using the fluorescent indicators Indo-1 (to measure [Ca2+]i) and SBFI (to measure [Na+]i). After electrical stimulation (either with action potentials or voltage-clamp pulses), some cells showed spontaneous Ca2+ release. The frequency of this release, where present, was variable. The Ca2+ content of the sarcoplasmic reticulum (SR) was measured by applying caffeine (10 mmol/L). The resulting increase of [Ca2+]i activated the electrogenic Na+-Ca2+ exchange, and the integral of this current was used to estimate the Ca2+ content of the SR. The SR Ca2+ content was significantly higher in cells that oscillated at high rates (>10 · min-1) than in those that were quiescent. The rate of removal of Ca2+ from the cytoplasm by non-SR mechanisms was measured by adding caffeine (10 mmol/L) and measuring the rate constant of decay of the resulting increase of [Ca2+]i. Cells that had a high rate constant of decay of [Ca2+]i had a low frequency of oscillations. Measurements of [Na+]i showed a positive correlation between the frequency of spontaneous SR Ca2+ release and [Na+]i. After cessation of stimulation, there was a gradual decrease of [Na+]i, which was correlated with a parallel decrease of the frequency of oscillation rate. We conclude that the variability of frequency of spontaneous SR Ca2+ release is due to variations of the rate of Ca2+ removal from the cell, which are probably due to Na+-Ca2+ exchange. The variability of Na+-Ca2+ exchange rate, in turn, is likely to result from variations of [Na+]i. (Circ Res. 1996;78:8S7-862.).
    Original languageEnglish
    Pages (from-to)857-862
    Number of pages5
    JournalCirculation research
    Volume78
    Issue number5
    DOIs
    Publication statusPublished - May 1996

    Keywords

    • Ca2+
    • Na+
    • Na+-Ca2+ exchange
    • Sarcoplasmic reticulum

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