Functional modifications of neuronal P/Q-type voltagedependent Ca 2ϩ channels expressed in Xenopus oocytes by oxidation were examined electrophysiologically. Oxidation by external H 2 O 2 enhanced the whole-oocyte currents through the Ca 2ϩ channels composed of the ␣1A, ␣2/␦, and ␤3 subunits at negative voltages (Ͻ0 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 H 2 O 2 to enhance the Ca 2ϩ channel activity did not require heterologous expression of the ␣2/␦ subunit, and it was not mimicked by a cysteine-specific oxidizing agent. The results suggest that oxidative stress may regulate the activity of neuronal Ca 2ϩ channels and that regulation by oxidation may be important in some clinical situations, such as in reperfusion injury after ischemic episodes.