PT  - JOURNAL ARTICLE
AU  - FR Jackson
AU  - J Gitschier
AU  - GR Strichartz
AU  - LM Hall
TI  - Genetic modifications of voltage-sensitive sodium channels in Drosophila: gene dosage studies of the seizure locus
AID  - 10.1523/JNEUROSCI.05-05-01144.1985
DP  - 1985 May 01
TA  - The Journal of Neuroscience
PG  - 1144--1151
VI  - 5
IP  - 5
4099  - http://www.jneurosci.org/content/5/5/1144.short
4100  - http://www.jneurosci.org/content/5/5/1144.full
SO  - J. Neurosci.1985 May 01; 5
AB  - 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.