Effect of sulfhydryl oxidation on ionic and gating currents associated with L-type calcium channels in isolated guinea-pig ventricular myocytes.
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.


CONCLUSIONS
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.
Lacampagne
A
A
Physiologie des Cellules Cardiaques et Vasculaires C.N.R.S. EP 21, Faculté des Sciences, Parc de Grandmont, Tours, France.
Duittoz
A
A
Bolaños
P
P
Peineau
N
N
Argibay
J A
JA
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D006168:Guinea Pigs; D015640:Ion Channel Gating / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010663:Phenylmercury Compounds / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D015220:Calcium Channels; D016877:Oxidants; D010663:Phenylmercury Compounds; D013438:Sulfhydryl Compounds; C002910:4-hydroxymercuribenzenesulfonate