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The Journal of Neuroscience, September 1, 1998, 18(17):6740-6747

Oxidation Regulates Cloned Neuronal Voltage-Dependent Ca²⁺ Channels Expressed in Xenopus Oocytes

Ai Li¹, Jacob Ségui¹, Stefan H. Heinemann², and Toshinori Hoshi¹

¹ Department of Physiology and Biophysics, Bowen 5660, The University of Iowa, Iowa City, Iowa 52242, and ² Max Planck Society, Research Unit Molecular and Cellular Biophysics, Jena, D-07747, Germany

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 1A, 2/, and 3 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 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 Ca²⁺ channels and that regulation by oxidation may be important in some clinical situations, such as in reperfusion injury after ischemic episodes.

Key words: Ca²⁺ channel; voltage-dependent gating; oxidation; hydrogen peroxide; voltage clamp; oocyte

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18176740-08$05.00/0

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