REGULATION OF BCL-XL CHANNEL ACTIVITY BY CALCIUM

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 sys tem. 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 s odium but not calcium and that Bcl-xl channel activity is reversibly i nhibited by luminal calcium with a half-dissociation constant of simil ar to 60 mu M This calcium-de pendent regulation of the Bcl-xl channel provides new insights into the roles of calcium and Bcl-2-related pro teins in the programmed cell death pathway.