Simultaneous recording of intramembrane charge movement components and calcium release in wild-type and S100A1−/− muscle fibres

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Blackwell Science Inc

RESUMO

In the preceding paper, we reported that flexor digitorum brevis (FDB) muscle fibres from S100A1 knock-out (KO) mice exhibit a selective suppression of the delayed, steeply voltage-dependent component of intra-membrane charge movement current termed Qγ. Here, we use 50 μm of the Ca2+ indicator fluo-4 in the whole cell patch clamp pipette, in addition to 20 mm EGTA and other constituents included for the charge movement studies, and calculate the SR Ca2+ release flux from the fluo-4 signals during voltage clamp depolarizations. Ca2+ release flux is decreased in amplitude by the same fraction at all voltages in fibres from S100A1 KO mice compared to fibres from wild-type (WT) littermates, but unchanged in time course at each pulse membrane potential. There is a strong correlation between the time course and magnitude of release flux and the development of Qγ. The decreased Ca2+ release in KO fibres is likely to account for the suppression of Qγ in these fibres. Consistent with this interpretation, 4-chloro-m-cresol (4–CMC; 100 μm) increases the rate of Ca2+ release and restores Qγ at intermediate depolarizations in fibres from KO mice, but does not increase Ca2+ release or restore Qγ at large depolarizations. Our findings are consistent with similar activation kinetics for SR Ca2+ channels in both WT and KO fibres, but decreased Ca2+ release in the KO fibres possibly due to shorter SR channel open times. The decreased Ca2+ release at each voltage is insufficient to activate Qγ in fibres lacking S100A1.

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