Journal of Neuroscience, Vol 5, 1144-1151, Copyright © 1985 by Society for Neuroscience
Genetic modifications of voltage-sensitive sodium channels in Drosophila: gene dosage studies of the seizure locus
FR Jackson, J Gitschier, GR Strichartz and LM Hall
We have identified a genetic locus in Drosophila melanogaster whose product
appears to have a structural role in the formation of functional
voltage-sensitive sodium channels. This locus, designated seizure, is
defined by two temperature-sensitive alleles (seits-1 and seits-2), each of
which causes convulsive seizures followed by a rapid but reversible
paralysis of adults at restrictive temperatures above 38 degrees C.
Previous work had shown that seits-2 extracts display an altered pH
dependence and an abnormally high Kd for [3H]-saxitoxin binding at high
temperatures, suggesting that sodium channels in seits- 2 mutants have an
altered structure (Jackson F. R., S. D. Wilson, G. R. Strichartz, and L. M.
Hall (1984) Nature 308: 189-191). These binding studies have now been
extended to extracts of seits-1 which have a Kd not significantly different
from wild-type at all assay temperatures. However, seits-1 extracts show a
reduced number of saxitoxin binding sites (Bmax) relative to wild-type.
This reduction is only 5 to 18% at 0 degree C but is 17 to 37% at 39
degrees C, suggesting that under certain conditions sodium channels in the
seits-1 mutant are more labile than those of wild-type. Cytogenetic studies
demonstrate that the seizure locus maps within region 60A to 60B8-10 on the
second chromosome. Gene dosage analysis of approximately 99.7% of the
genome, including this second chromosome region, failed to detect a
wild-type locus whose dose affected saxitoxin-binding activity.
Nevertheless, the mutant seits-2 allele has codominant and dose-dependent
effects on paralytic behavior and saxitoxin-binding activity.(ABSTRACT
TRUNCATED AT 250 WORDS)
Previous Article | Next Article
