Critical residues of the Caenorhabditis elegans unc-2 voltage-gated calcium channel that affect behavioral and physiological properties

Eleanor A. Mathews, Esperanza García, Celia M. Santi, Gregory P. Mullen, Colin Thacker, Donald G. Moerman, Terrance P. Snutch

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

The Caenorhabditis elegans unc-2 gene encodes a voltage-gated calcium channel α1 subunit structurally related to mammalian dihydropyridine-insensitive high-threshold channels. In the present paper we describe the characterization of seven alleles of unc-2. Using an unc-2promoter-tagged green fluorescent protein construct, we show that unc-2 is primarily expressed in motor neurons, several subsets of sensory neurons, and the HSN and VC neurons that control egg laying. Examination of behavioral phenotypes, including defecation, thrashing, and sensitivities to aldicarb and nicotine suggests that UNC-2 acts presynaptically to mediate both cholinergic and GABAergic neurotransmission. Sequence analysis of the unc-2 alleles shows that e55, ra605, ra606, ra609, and ra610 all are predicted to prematurely terminate and greatly reduce or eliminate unc-2 function. In contrast, the ra612 and ra614 alleles are missense mutations resulting in the substitution of highly conserved residues in the C terminus and the domain IVS4-IVS5 linker, respectively. Heterologous expression of a rat brain P/Q-type channel containing the ra612 mutation shows that the glycine to arginine substitution affects a variety of channel characteristics, including the voltage dependence of activation, steady-state inactivation, as well as channel kinetics. Overall, our findings suggest that UNC-2 plays a pivotal role in mediating a number of physiological processes in the nematode and also defines a number of critical residues important for calcium channel function in vivo.

Original languageEnglish
Pages (from-to)6537-6545
Number of pages9
JournalJournal of Neuroscience
Volume23
Issue number16
DOIs
StatePublished - Jul 23 2003

Keywords

  • Behavior
  • C. elegans
  • Calcium channel
  • Electrophysiology
  • Mutation
  • Presynaptic

Fingerprint

Dive into the research topics of 'Critical residues of the Caenorhabditis elegans unc-2 voltage-gated calcium channel that affect behavioral and physiological properties'. Together they form a unique fingerprint.

Cite this