The brain-specific beta4 subunit downregulates BK channel cell surface expression

Sonal Shruti, Joanna Urban-Ciecko, James A. Fitzpatrick, Robert Brenner, Marcel P. Bruchez, Alison L. Barth

Research output: Contribution to journalArticle

50 Scopus citations

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 β4 alters channel Ca ++- and voltage-sensitivity, and β4 knock-out animals exhibit spontaneous seizures. Here we investigate β4's effect on BK channel trafficking to the plasma membrane. Using a novel genetic tag to track the cellular location of the pore-forming BKα subunit in living cells, we find that β4 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 β4 expression, whole-cell BK channel currents display none of the characteristic properties of BKα+β4 channels observed in heterologous cells. Finally, β4 knock-out animals exhibit a 2.5-fold increase in whole-cell BK channel current, indicating that β4 also regulates current magnitude in vivo. Thus, we propose that a major function of the brain-specific β4 subunit in CA3 neurons is control of surface trafficking.

Original languageEnglish
Article numbere33429
JournalPloS one
Volume7
Issue number3
DOIs
StatePublished - Mar 16 2012
Externally publishedYes

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    Shruti, S., Urban-Ciecko, J., Fitzpatrick, J. A., Brenner, R., Bruchez, M. P., & Barth, A. L. (2012). The brain-specific beta4 subunit downregulates BK channel cell surface expression. PloS one, 7(3), [e33429]. https://doi.org/10.1371/journal.pone.0033429