1. Archive
2. Vol.54, No.3

Characterization of Junctional Sarcoplasmic Reticulum Ca² Content and Release by Short-Term Mechanical Restitution in Cardiac Muscle

Abstract: To study Ca² handling by the junctional sarcoplasmic reticulum (JSR), the time course of short-term mechanical restitution after varying magnitudes of twitch contractions was assessed in rat papillary muscle. Mechanical restitution consisted of a pretwitch latency period followed by a rapid and a subsequent much slower restitution of twitch force. The rate of rapid restitution was independent of the magnitude of the preceding twitch, which suggests that the rate of JSR Ca² repletion was dependent on the amount of Ca² remaining in the JSR after a twitch contraction. Based on this finding, the functions G(t) and H(t), representing the time courses of JSR Ca² repletion and release, respectively, were derived graphically from a family of the mechanical restitution curves. G(t) increased monotonically with time at a decreasing rate, while H(t) increased with time in a sigmoid manner. The mechanical alternans were simulated by using experimental values and mathematically predicted values of G(t) and H(t). A substitution of extracellular Na with Li to inhibit Na/Ca² exchange resulted in an augmentation of G(t) by approximately 10%, presumably by increasing the tubular SR Ca² uptake. The inhibition of tubular SR Ca² uptake by thapsigargin (10 μM) reduced mechanical restitution by approximately 13% of the maximal twitch force, independent of the phase of mechanical restitution; the effect was greater at an earlier time point in the mechanical restitution. These results suggest that early JSR Ca² replenishment results mainly from the movement of Ca² from the tubular SR.

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