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

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.

Pubmed ID: 22438928

Authors

  • Shruti S
  • Urban-Ciecko J
  • Fitzpatrick JA
  • Brenner R
  • Bruchez MP
  • Barth AL

Journal

PloS one

Publication Data

March 22, 2012

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS052574
  • Agency: NCRR NIH HHS, Id: U54 RR022241

Mesh Terms

  • Animals
  • Brain
  • CA3 Region, Hippocampal
  • Calcium Signaling
  • Cell Membrane
  • Down-Regulation
  • Electrophysiological Phenomena
  • Endoplasmic Reticulum
  • Female
  • HEK293 Cells
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channels
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Neurological
  • Protein Subunits
  • Recombinant Proteins