The hypothesis that sarcoplasmic reticulum (SR) generates subsarcolemmal [Ca] higher than that in the bulk of sarcoplasm and that it affects the rate of Na+Ca exchange were tested. Voltage clamped cardiomyocytes of guinea-pigs and rats were stimulated by pre-pulses from a holding potential of -80 mV to -40 mV (20 ms) followed by 200 ms depolarizations to +5 mV. Single 5, 10, 20, 30, 50, 100 and 300 ms depolarizations were interposed between 200 ms pulses. The amplitude of the tail (Na/Ca exchange) currents recorded upon repolarization were compared with instantaneous fluorescence on Indo 1 loaded into cells. In both species amplitude of the tail currents were higher during the ascending phase of the Ca transient than during the descending phase, although the fluorescence was lower. The dissociation was abolished by thapsigargin (TG), the blocker of the SR Ca-ATPase. The results suggest that over the initial < 50 ms of the transient the Na/Ca exchangers are exposed to [Ca] higher than that in the bulk sarcoplasm and that it is generated by the SR.
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