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J Biol Chem, Vol. 273, Issue 28, 17307-17310, July 10, 1998

COMMUNICATION
Regulation of Bcl-xl Channel Activity by Calcium

Minh Lam, Manjunatha B. Bhat^§, Gabriel Nuñez^¶, Jianjie Ma^§, and Clark W. Distelhorst^**

From the Departments of ^** Medicine,  Pharmacology, and ^§ Physiology and Biophysics, Case Western Reserve University, Cleveland,Ohio 44106 and the ^¶ Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109

Recent studies have demonstrated that the anti-apoptotic proteins, Bcl-2 and Bcl-xl, with the carboxyl-terminal hydrophobic domain removed, form cation-selective channels in the lipid bilayer reconstitution system. However, the regulatory properties of these channels are unknown. In this study, we investigated the ion-conducting properties of full-length Bcl-xl in the lipid bilayer reconstitution system. Our findings indicate that Bcl-xl forms a cation-selective channel that conducts sodium but not calcium and that Bcl-xl channel activity is reversibly inhibited by luminal calcium with a half-dissociation constant of ~60 µM. This calcium-dependent regulation of the Bcl-xl channel provides new insights into the roles of calcium and Bcl-2-related proteins in the programmed cell death pathway.

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Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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