Résumé :
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In skeletal muscle, contraction is induced by a massive release of calcium from the sarcoplasmic reticulum (SR) in response to depolarization of the cell. Duringsustained depolarization, a voltage-activated calcium influx is also known to occur while calcium depletion of the SR activates a sarcolemmal store-operated calciuminflux. Additionally, early experiments in frog skeletal muscle have shown that excitation-contraction coupling requires external calcium to function (Brum et al., 1988,J. Physiol., 398:475-505). In the present study, we evoked SR calcium leak by exposing isolated mouse skeletal muscle fibers to the SR calcium ATPase inhibitorcyclopiazonic acid (CPA) under voltage control. CPA poisoning induced a progressive intracellular calcium increase monitored with the calcium dye fura-2 that wasreversibly reduced upon removal of external calcium at a holding potential of -80 mV. At first sight, this result suggested that a calcium influx partly contributed to theincrease in intracellular calcium produced by CPA. However, this effect was still observed at a holding potential of +40 mV for which the electrochemical gradient in favorof calcium influx should be very low, suggesting that the rate of SR calcium leak was dependent on the presence of calcium in the external medium. CPA-evoked SRcalcium leak was significantly increased in dystrophin-deficient muscle fibers. Effects of external calcium on CPA-evoked SR calcium leak and on calcium influx measuredby the manganese quenching method are currently investigated in dystrophin-deficient muscle fibers.
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