Abstract
Calcium- and voltage-gated (BK) K(+) channels encoded by Slo1 play an essential role in nervous systems. Although it shares many common features with voltage-dependent K(V) channels, the BK channel exhibits differences in gating and inactivation. Using a mutant in which FWI replaces three residues (FIW) in the NH(2) terminus of wild-type beta2-subunits, in conjunction with alanine-scanning mutagenesis of the Slo1 S6 segment, we identify that the NH(2) terminus of beta2-subunits interacts with the residues near the cytosolic superficial mouth of BK channels during inactivation. The cytosolic blockers did not share the sites with NH(2) terminus of beta2-subunits. A novel blocking-inactivating scheme was proposed to account for the observed non-competition inactivation. Our results also suggest that the residue Ile-323 plays a dual role in interacting with the NH(2) terminus of beta2-subunits and modulating the gating of BK channels.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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DNA Mutational Analysis
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Humans
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Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / chemistry
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Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / genetics
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Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / metabolism*
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Large-Conductance Calcium-Activated Potassium Channel beta Subunits* / chemistry
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Large-Conductance Calcium-Activated Potassium Channel beta Subunits* / genetics
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Large-Conductance Calcium-Activated Potassium Channel beta Subunits* / metabolism
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Mice
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Models, Molecular
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Molecular Sequence Data
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Molecular Structure
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Mutagenesis, Site-Directed
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Patch-Clamp Techniques
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Protein Structure, Tertiary*
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Sequence Alignment
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Xenopus laevis
Substances
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Kcnma1 protein, mouse
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Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
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Large-Conductance Calcium-Activated Potassium Channel beta Subunits