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PLoS One. 2012;7(3):e33429. doi: 10.1371/journal.pone.0033429. Epub 2012 Mar 16.

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

Author information

1
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.

Erratum in

  • PLoS One. 2012 May;7(5): doi/10.1371/annotation/64524ba8-f739-4fa8-93bf-862b160dca5c.

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.

PMID:
22438928
PMCID:
PMC3306404
DOI:
10.1371/journal.pone.0033429
[Indexed for MEDLINE]
Free PMC Article
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