In vivo functional role of the Drosophila hyperkinetic beta subunit in gating and inactivation of Shaker K+ channels

J W Wang; C F Wu

doi:10.1016/S0006-3495(96)79510-3

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In vivo functional role of the Drosophila hyperkinetic beta subunit in gating and inactivation of Shaker K+ channels

Journal article

Open access

Peer reviewed

In vivo functional role of the Drosophila hyperkinetic beta subunit in gating and inactivation of Shaker K+ channels

J W Wang and C F Wu

Biophysical journal, Vol.71(6), pp.3167-3176

12/1996

DOI: 10.1016/S0006-3495(96)79510-3

PMCID: PMC1233805

PMID: 8968587

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Abstract

The physiological roles of the beta, or auxiliary, subunits of voltage-gated ion channels, including Na+, Ca2+, and K+ channels, have not been demonstrated directly in vivo. Drosophila Hyperkinetic (Hk) mutations alter a gene encoding a homolog of the mammalian K+ channel beta subunit, providing a unique opportunity to delineate the in vivo function of auxiliary subunits in K+ channels. We found that the Hk beta subunit modulates a wide range of the Shaker (Sh) K+ current properties, including its amplitude, activation and inactivation, temperature dependence, and drug sensitivity. Characterizations of the existing mutants in identified muscle cells enabled an analysis of potential mechanisms of subunit interactions and their functional consequences. The results are consistent with the idea that via hydrophobic interaction, Hk beta subunits modulate Sh channel conformation in the cytoplasmic pore region. The modulatory effects of the Hk beta subunit appeared to be specific to the Sh alpha subunit because other voltage- and Ca(2+)-activated K+ currents were not affected by Hk mutations. The mutant effects were especially pronounced near the voltage threshold of IA activation, which can disrupt the maintenance of the quiescent state and lead to the striking neuromuscular and behavioral hyperexcitability previously reported.

Mutagenesis

Membrane Potentials - drug effects

Drosophila Proteins

Potassium Channels - biosynthesis

Temperature

Drosophila

Potassium Channels - physiology

Electric Conductivity

Cytoplasm - physiology

Cell Membrane - physiology

Macromolecular Substances

Patch-Clamp Techniques

Animals

Larva

Time Factors

Potassium Channels - chemistry

Kinetics

Potassium Channel Blockers

Shaker Superfamily of Potassium Channels

Ion Channel Gating

4-Aminopyridine - pharmacology

Details

Title: Subtitle: In vivo functional role of the Drosophila hyperkinetic beta subunit in gating and inactivation of Shaker K+ channels
Creators: J W Wang - Department of Biological Sciences, University of Iowa, Iowa City 52242, USA
C F Wu
Resource Type: Journal article
Publication Details: Biophysical journal, Vol.71(6), pp.3167-3176
DOI: 10.1016/S0006-3495(96)79510-3
PMID: 8968587
PMCID: PMC1233805
NLM abbreviation: Biophys J
ISSN: 0006-3495
eISSN: 1542-0086
Publisher: United States
Grant note: NS 26528 / NINDS NIH HHS NS18500 / NINDS NIH HHS
Language: English
Date published: 12/1996
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9984070769702771

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