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Journal of Neuroscience, Vol 10, 1357-1371, Copyright © 1990 by Society for Neuroscience
A voltage-clamp analysis of gene-dosage effects of the Shaker locus on larval muscle potassium currents in Drosophila
FN Haugland and CF Wu
Department of Biology, University of Iowa, Iowa City 52242.
Mutations of the Shaker (Sh) locus of Drosophila reduce, eliminate, or
otherwise alter a transient potassium current, IA, in muscle. Recent
molecular studies indicate that the Sh locus produces several proteins by
alternative splicing, but the relationships of the variety of Sh gene
products to IA channels in the various excitable membranes still remain to
be determined. In Drosophila, many enzymes have been shown to exhibit
gene-dosage effects; their amounts vary in direct proportion to the number
of structural genes present. We describe a physiological isolation of IA in
larval muscle which allowed precise quantification of gene-dosage effects
on IA in Sh heterozygotes and aneuploids. We found that doubling the number
of Sh genes in aneuploids increased IA to twice that of normal, consistent
with the notion that the Sh locus encodes the entire IA channel in larval
muscle. We further examined heterozygous combinations of different Sh
mutations for evidence of interactions among Sh gene products within the IA
channel, which may yield clues to the possible subunit composition of the
channel. Combinations among 5 Sh mutations plus their normal counterpart
followed a simple gene-dosage effect; in each case the resulting IA was
about the average of the homozygous currents, compatible with the notion of
additive contributions from 2 independent populations of IA channels. Two
additional Sh mutations caused pronounced departures from the simple dosage
effect; the amplitude of IA in heterozygotes was significantly smaller than
that expected from gene dosage, a strong dominant effect attributable to
interactions among protein subunits. These contrasting observations may be
accounted for by certain hetero- or homo-multimeric arrangements of Sh
products in the IA channel.
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