All-or-None Effect of γ1 Auxiliary Subunit on BK Channel Gating

Abstract

Ca2+-and-voltage-gated K+-channels (BK) are symmetrical complexes whose minimal functional unit is a tetramer composed of four identical α-subunits. BK α-subunits can coassemble with auxiliary subunits which drastically influence channel gating. Two families of BK auxiliary subunits have been described, β and γ subunits. Up to four β-subunits can assemble with the α-subunits in a BK channel complex, where each individual β-subunit contributes an identical additive increment to the total β-induced gating shift. At present, the stoichiometry of the assembly of α and γ subunits is unknown. Here we show that, in contrast to gating shifts produced by β-subunits, the γ1-effect on BK channel is an 'all-or-none' type of functional regulation. The presence of a single γ1 subunit in BK channels is enough to produce the full γ1-induced gating shift, although probably more than one γ1 can assemble in a BK channel complex. Our results describe an uncommon example of asymmetric functional regulation of a symmetric oligomeric protein. (Supported by NRSA F32 GM103138 to VGP and GM081748 to CJL).