Oxidation regulates cloned neuronal voltage-dependent Ca2+ channels expressed in Xenopus oocytes.
Functional modifications of neuronal P/Q-type voltage-dependent Ca2+ channels expressed in Xenopus oocytes by oxidation were examined electrophysiologically. Oxidation by external H2O2 enhanced the whole-oocyte currents through the Ca2+ channels composed of the alpha1A, alpha2/delta, and beta3 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 alpha2/delta 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.
Department of Physiology and Biophysics, Bowen 5660, The University of Iowa, Iowa City, Iowa 52242, USA.
A
A
Li
J
J
Ségui
S H
SH
Heinemann
T
T
Hoshi
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D003001:Cloning, Molecular; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D013439:Sulfhydryl Reagents; D014981:Xenopus
D015220:Calcium Channels; D011725:Pyridines; D013439:Sulfhydryl Reagents; C011801:2,2'-dithiobis(5-nitropyridine); D006861:Hydrogen Peroxide