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Effect of sulfhydryl oxidation on ionic and gating currents associated with L-type calcium channels in isolated
A Lacampagne1, A Duittoz, P Bolaños
1Physiologie des Cellules Cardiaques et Vasculaires C.N.R.S. EP 21, Faculté des Sciences, Parc de Grandmont, Tours, France.
Objective:
L-type calcium currents (ICa) and gating currents modification by extracellular application of the selective free sulfhydryl oxidant p-hydroxy-mercuric-phenylsulphonic acid (PHMPS) were studied.
Methods:
Both currents were obtained with the whole cell patch clamp technique in guinea-pig ventricular cardiocytes.
Results:
The main finding was a reduction of ICa clearly differentiable from a "run down" process. This effect was protected, stopped and in some cases partially reversed by dithiothreitol, a protective reagent for -SH groups. We also found a decrease of the gating currents associated with L-type calcium channels. The calcium modulation and cAMP phosphorylation systems of ICa are unaffected by PHMPS. With barium as charge carrier the current-voltage curves of barium currents were shifted by 10 mV to the positive direction by PHMPS. The same effect was obtained with calcium currents using BAPTA as a fast calcium buffer.
Conclusion:
The results indicate that oxidation of -SH groups carried by the channel protein induces dysfunction of the calcium entry to cardiac cells by altering the gating process. A participation of thiol functions on the gating of the calcium channel is proposed.