Electrophysiological study on the physiological roles of the oscillatory release of calcium from the sarcoplasmic reticulum in myocardium.

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The electrical and mechanical activities related to the oscillatory release of Ca from the sarcoplasmic reticulum (SR) were studied in muscle preparations and single myocytes isolated from guinea-pig ventricles. In partially depolarized papillary muscles, rapid stimulation (1 Hz) in the presence of <beta>-adrenergic stimulants induced oscillatory afterpotentials (OAP) and aftercontractions (AC) which were produced by the oscillatory release of Ca from SR. Mg ions at concentrations of 5-12 mM were found to suppress these OAP and AC. However, Mg potentiated the twitch contractions, and this effect was due to suppression of the oscillatory release of Ca from SR during diastole. Thus, the Ca oscillation at SR appeared to decrease the amount of Ca in SR avaliable for twitch. Since microscopic Ca oscillations may be present even in normal myocardium, the above results suggest that such oscillaltions can be an important mechanism regulating the amount of Ca in SR as well as the cellular Ca ho … More meostasis, provided there is a link between these oscillations and the Ca-extruding function of the sarcolemma. In voltage-clamped isolated myocytes, high concentrations (15-25 mM) of caffeine, which releases Ca from SR, were found to induce pulse-like small (20-30 pA at the resting potential) inward currents. These currents appeard to be activated by the intracellular Ca, since Ca injection into the cell or application of large depolarizations which produced a tonic tension enhanced them. The currents were Na-dependent but could flow in the presence of Li instead of Na. The pulse-like development suggested that the currents were generated in the membrane sites which distributed relatively scarcely in the sarcolemma. The most probable sites are those facing the juxtamembranous SR. observed currents might reflect one aspect of the functional coupling of the sarcolemma and SR. We are now further studying the nature of these currents. Another type of the Ca-activated electrical event was also noted in isolated myocytes with the patch clamp technique. This was the current through the Ca-activated non-specific cation channel, and its properties were quantiatively analyzed. This current contributes to the Ca-mediated steady background conductance and does not generate pulse-like electrical events in the whole cell level. Less