On the overshoot of calcium accumulation in fragmented sarcoplasmic reticulum induced by thymol

The mechanism was studied of the overshoot of calcium accumulation in fragmented sarcoplasmic reticulum (FSR) which is observed when the active transport of calcium into FSR is performed in the presence of thymol; the amount of calcium in FSR increases steeply during the first minute of the reaction and then decreases markedly. In contrast to this behavior, the amount of calcium in FSR increases monotonically and then reaches saturation in the absence of thymol. It is shown that the amount of calcium accumulated in FSR is determined by the balance between the rapid influx and efflux of calcium, and that both processes are depressed by thymol. The overshoot of calcium accumulation can be explained as follows: thymol so markedly depresses the efflux of calcium uncoupled with Ca2+-ATPase activity that the amount of calcium is increased in FSR in spite of partial deactivation of Ca2+-ATPase. However, the state of the FSR membrane is rapidly changed when the concentration of accumulated calcium exceeds a certain critical value. Concomitant with this change, the calcium permeability of the membrane is increased, leading to a decrease in the amount of accumulated calcium. The effects of magnesium and temperature on the overshoot of calcium accumulation can be accounted for by this proposed mechanism.