Molecular basis of junctional current rectification at an electrical synapse.

Rectifying electrical synapses (RESs) exist across animal species, but their rectification mechanism is largely unknown. We investigated why RESs between AVA premotor interneurons and A-type cholinergic motoneurons (A-MNs) in Caenorhabditis elegans escape circuit conduct junctional currents (I j) only in the antidromic direction. These RESs consist of UNC-7 innexin in AVA and UNC-9 innexin in A-MNs. UNC-7 has multiple isoforms differing in the length and sequence of the amino terminus. In a heterologous expression system, only one UNC-7 isoform, UNC-7b, can form heterotypic gap junctions (GJs) with UNC-9 that strongly favor I j in the UNC-9 to UNC-7 direction. Knockout of unc-7b alone almost eliminated the I j, whereas AVA-specific expression of UNC-7b substantially rescued the coupling defect of unc-7 mutant. Neutralizing charged residues in UNC-7b amino terminus abolished the rectification property of UNC-7b/UNC-9 GJs. Our results suggest that the rectification property results from electrostatic interactions between charged residues in UNC-7b amino terminus.