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Defining the BK channel domains required for beta1-subunit modulation.


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.

SUBMITTER: Morrow JP 

PROVIDER: S-EPMC1458800 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

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Defining the BK channel domains required for beta1-subunit modulation.

Morrow John P JP   Zakharov Sergey I SI   Liu Guoxia G   Yang Lin L   Sok Andrea J AJ   Marx Steven O SO  

Proceedings of the National Academy of Sciences of the United States of America 20060320 13


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 mu  ...[more]

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