| 19651766 |
Prosser BL, Hernandez-Ochoa EO, Zimmer DB, Schneider MF: Simultaneous recording of intramembrane charge movement components and calcium release in wild-type and S100A1-/- muscle fibres. J Physiol. 2009 Sep 15;587(Pt 18):4543-59. Epub 2009 Aug 3.
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 Q (gamma). Here, we use 50 microm of the Ca (2+) 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 Ca (2+) release flux from the fluo-4 signals during voltage clamp depolarizations. Ca (2+) 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 Q (gamma). The decreased Ca (2+) release in KO fibres is likely to account for the suppression of Q (gamma) in these fibres. Consistent with this interpretation, 4-chloro-m-cresol (4-CMC; 100 microm) increases the rate of Ca (2+) release and restores Q (gamma) at intermediate depolarizations in fibres from KO mice, but does not increase Ca (2+) release or restore Q (gamma) at large depolarizations. Our findings are consistent with similar activation kinetics for SR Ca (2+) channels in both WT and KO fibres, but decreased Ca (2+) release in the KO fibres possibly due to shorter SR channel open times. The decreased Ca (2+) release at each voltage is insufficient to activate Q (gamma) in fibres lacking S100A1. |
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