The Eag Family of K+ Channels in Drosophila and Mammals
Mutations of eag, first identified in Drosophila on the basis of their leg‐shaking phenotype, cause repetitive firing and enhanced transmitter release in motor neurons. The encoded EAG polypeptide is related both to voltage‐gated K+ channels and to cyclic nucleotide‐gated cation channels. Homology s...
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Published in | Annals of the New York Academy of Sciences Vol. 868; no. 1; pp. 356 - 369 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.04.1999
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Subjects | |
Online Access | Get full text |
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Summary: | Mutations of eag, first identified in Drosophila on the basis of their leg‐shaking phenotype, cause repetitive firing and enhanced transmitter release in motor neurons. The encoded EAG polypeptide is related both to voltage‐gated K+ channels and to cyclic nucleotide‐gated cation channels. Homology screens identified a family of eag‐related channel polypeptides, highly conserved from nematodes to humans, comprising three subfamilies: EAG, ELK, and ERG. When expressed in frog oocytes, EAG channels behave as voltage‐dependent, outwardly rectifying K+‐selective channels. Mutations of the human eag‐related gene (HERG) result in a form of cardiac arrhythmia that can lead to ventricular fibrillation and sudden death. Electrophysiological and pharmacological studies have provided evidence that HERG channels specify one component of the delayed rectifier, IKr, that contributes to the repolarization phase of cardiac action potentials. An important role or HERG channels in neuronal excitability is also suggested by the expression of these channels in brain tissue. Moreover, mutations of ERG‐type channels in the Drosophila sei mutant cause temperature‐induced convulsive seizures associated with aberrant bursting activity in the flight motor pathway. The in vivo function of ELK channels has not yet been established, but when these channels are expressed in frog oocytes, they display properties intermediate between those of EAG‐ and ERG‐type channels. Coexpression of the K+‐channel b subunit encoded by Hk with EAG in oocytes dramatically increases current amplitude and also affects the gating and modulation of these currents. Biochemical evidence indicates a direct physical interaction between EAG and HK proteins. Overall, these studies highlight the diverse properties of the eag family of K+ channels, which are likely to subserve diverse functions in vivo. |
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Bibliography: | ark:/67375/WNG-0XNSZS7L-N istex:9C5DA6D88F7DD90E378C881D8A8D2C7F0BBC0BD2 ArticleID:NYAS356 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0077-8923 1749-6632 |
DOI: | 10.1111/j.1749-6632.1999.tb11297.x |