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Journal of Neuroscience, Vol 13, 4669-4679, Copyright © 1993 by Society for Neuroscience
Modulation of different K+ currents in Drosophila: a hypothetical role for the Eag subunit in multimeric K+ channels
Y Zhong and CF Wu
Department of Biology, University of Iowa, Iowa City 52242.
We examined the role of the ether a go-go (eag) gene in modulation of K+
currents and the possibility of its protein product Eag as a subunit in the
heteromultimeric assembly of K+ channels by voltage-clamp analysis of
larval muscle membrane currents. Previous DNA sequence studies indicate
that the eag gene codes for a polypeptide homologous to, but distinct from,
the Shaker (Sh) K+ channel subunits (Warmke et al., 1991), and
electrophysiological recordings revealed allele- specific effects of eag on
four identified K+ currents in Drosophila larval muscles (Zhong and Wu,
1991). Further studies of eag alleles indicated that none of the eag
mutations, including alleles producing truncated mRNA messages, eliminate
any of the four K+ currents, and that the mutational effects exhibit strong
temperature dependence. We found that both W7, an antagonist of
Ca2+/calmodulin, and cGMP analogs modulated K+ currents and that their
actions were altered or even abolished by eag mutations. These results
suggest a role of eag in modulation of K+ currents that may subserve
integration of signals at a converging site of the two independent
modulatory pathways. The Sh locus is known to encode certain subunits of
the IA channel in larval muscle. The existence of multiple eag and Sh
alleles enabled an independent test of the idea of Eag as a K+ channel
subunit by studying IA in different double-mutant combinations. An array of
allele-specific interaction between eag and Sh was observed, which reflects
a close association between the Sh and eag subunits within the IA channel.
Taken together, our data strengthen the possibility that the eag locus
provides a subunit common to different K+ channels. The role of the eag
subunit for modulating channels, as opposed to that of Sh subunits required
for gating, selectivity, and conductance of the channel, suggest a
combinatorial genetic framework for generating diversified K+ channels.
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