Genetic modifications of voltage-sensitive sodium channels in Drosophila: gene dosage studies of the seizure locus.

Abstract

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)

• Authors: F R Jackson, J Gitschier, G R Strichartz, L M Hall
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 5 Issue 5 Pg. 1144-51 (May 1985) ISSN: 0270-6474 [Print] United States
• PMID: 2582101 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ion Channels

Topics

• Animals
• Drosophila melanogaster (genetics)
• Genes
• Genotype
• Ion Channels
• Seizures (genetics)