Defining the BK channel domains required for beta1-subunit modulation

Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5096-101. doi: 10.1073/pnas.0600907103. Epub 2006 Mar 20.

Abstract

In a wide variety of cell types, including neurons and smooth muscle cells, activation of the large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels causes transient membrane hyperpolarization, thereby regulating cellular excitability. Similar to other voltage-gated ion channels, BK channels, a tetramer of alpha-subunits, associate with auxiliary beta-subunits in a tissue-specific manner, modifying the channel's gating properties. The BK beta1-subunit, which is expressed in smooth muscle, increases the apparent Ca(2+) sensitivity (marked by a hyperpolarizing shift in the conductance-voltage relationship at a given Ca(2+) concentration), slows macroscopic activation and deactivation, and is required for channel activation by 17beta-estradiol. The beta1-subunit is essential for normal regulation of vascular smooth muscle contractility and blood pressure. Little is known, however, about the molecular mechanisms of beta1-subunit modulation of alpha-subunits. Here we show that the beta1-subunit's modulation of the Ca(2+) and 17beta-estradiol sensitivities can be dissociated from its effects on gating kinetics by truncation of the alpha-subunit's extracellular N-terminal residues. The BK alpha-subunit N terminus interacts uniquely with the beta1-subunit: beta2 regulation of the alpha-subunit is unaltered by truncation of the N terminus. Although the functional interaction of alpha and beta1 requires the N-terminal tail of alpha, the physical association requires the S1, S2, and S3 transmembrane helices of alpha.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Electrophysiology
  • Estradiol / pharmacology
  • Humans
  • Ion Channel Gating
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • Mutation / genetics
  • Patch-Clamp Techniques
  • Potassium Channels, Calcium-Activated / chemistry*
  • Potassium Channels, Calcium-Activated / genetics
  • Potassium Channels, Calcium-Activated / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*

Substances

  • Potassium Channels, Calcium-Activated
  • Protein Subunits
  • Estradiol