The brain-specific Beta4 subunit downregulates BK channel cell surface expression.

ABSTRACT: The large-conductance K(+) channel (BK channel) can control neural excitability, and enhanced channel currents facilitate high firing rates in cortical neurons. The brain-specific auxiliary subunit ?4 alters channel Ca(++)- and voltage-sensitivity, and ?4 knock-out animals exhibit spontaneous seizures. Here we investigate ?4's effect on BK channel trafficking to the plasma membrane. Using a novel genetic tag to track the cellular location of the pore-forming BK? subunit in living cells, we find that ?4 expression profoundly reduces surface localization of BK channels via a C-terminal ER retention sequence. In hippocampal CA3 neurons from C57BL/6 mice with endogenously high ?4 expression, whole-cell BK channel currents display none of the characteristic properties of BK?+?4 channels observed in heterologous cells. Finally, ?4 knock-out animals exhibit a 2.5-fold increase in whole-cell BK channel current, indicating that ?4 also regulates current magnitude in vivo. Thus, we propose that a major function of the brain-specific ?4 subunit in CA3 neurons is control of surface trafficking.

SUBMITTER: Shruti S 

PROVIDER: S-EPMC3306404 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature