Oxidation regulates cloned neuronal voltage-dependent Ca2+ channels expressed in Xenopus oocytes

Abstract

Functional modifications of neuronal P/Q-type voltage-dependent Ca2+ channels expressed in Xenopus oocytes by oxidation were examined electrophysiologically. Oxidation by external H202 enhanced the whole-oocyte currents through the Ca2+ channels composed of the α1A, α2/δ, and β3 subunits at negative voltages (<0 mV) without markedly affecting the currents at more positive voltages. Single-channel analysis showed that oxidation accelerates the overall channel opening process. The effect of H2O2 to enhance the Ca2+ channel activity did not require heterologous expression of the α2/δ subunit, and it was not mimicked by a cysteine-specific oxidizing agent. The results suggest that oxidative stress may regulate the activity of neuronal Ca2+ channels and that regulation by oxidation may be important in some clinical situations, such as in reperfusion injury after ischemic episodes.