Carboxy Terminus Splice Variation Alters CIC Channel Gating and Extracellular Cysteine Reactivity

ABSTRACT

CLH-3a and CLH-3b are Caenorhabditis elegans CIC channel splice variants that exhibit striking differences in voltage, Cl-, and H+ sensitivity. The major primary structure differences between the channels include a 71 amino acid CLH-3a N-terminal extension and a 270 amino acid extension of the CLH-3b C-terminus. Deletion of the CLH-3a N-terminus or generation of a CLH-3a/b chimera has no effect on channel gating. In contrast, deletion of a 169 amino acid C-terminal CLH-3b splice insert or deletion of the last 11 amino acids of cystathionine-β-synthase domain 1 gives rise to functional properties identical to those of CLH-3a. Voltage-, Cl-, and H+-dependent gating of …