Glutamate-gated chloride channels (GluCls) mediate fast inhibitory neurotransmission in invertebrate nervous systems. Insect GluCls show alternative splicing but its impact on channel function and pharmacology remains to be determined. We have isolated GluCl cDNAs from larvae of the silkworm (Bombyx mori) showing that 6 BmGluCl variants are generated by splicing in exons 3 and 9. When expressed in Xenopus laevis oocytes, the three exon 3 variants (3a, b, c) had similar EC50 values for L-glutamate and ivermectin (IVM); however, the maximum L-glutamate- and IVM-induced response of the channels differed strikingly between variants, with the 3c variant showing the largest L-glutamate- and IVM-induced responses. Binding assays using [3H]IVM indicate that diversity in IVM responses among the GluCl variants are mainly due to the impact on channel assembly. We have identified 4 amino acids in exon 3c as hot spots determining the highest amplitude of the L-glutamate- and IVM-induced responses.

Exon 3 splicing and mutagenesis identify residues influencing cell surface density of heterologously-expressed silkworm (<i>Bombyx mori</i>) glutamate-gated chloride channels

248th National Meeting (2014)

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Exon 3 splicing and mutagenesis identify residues influencing cell surface density of heterologously-expressed silkworm (Bombyx mori) glutamate-gated chloride channels