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

Cardiovasc Res. 1995 Nov;30(5):799-806.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Cells, Cultured
  • Guinea Pigs
  • Ion Channel Gating / drug effects*
  • Myocardium / metabolism*
  • Oxidants / pharmacology*
  • Patch-Clamp Techniques
  • Phenylmercury Compounds / pharmacology*
  • Sulfhydryl Compounds / pharmacology*

Substances

  • Calcium Channels
  • Oxidants
  • Phenylmercury Compounds
  • Sulfhydryl Compounds
  • 4-hydroxymercuribenzenesulfonate