Alternative splicing in the synaptic protein interaction site of rat Ca(v)2.2 (alpha (1B)) calcium channels: changes induced by chronic inflammatory pain

Abstract

Voltage-gated N-type Ca(2+) channels play a central role in regulation of neurotransmitter release. The II-III linker of N-type calcium channel alpha(1B) subunit (exons 17-21 in rats) contains synaptic protein interaction (synprint) site, which plays a pivotal role in efficient neurotransmission. Using RT-PCR analysis of rat hippocampus and lumbar spinal cord transcripts, the expressions of Ca(v)2.2 exon 18a and a novel Ca(v)2.2 splice variant, which were detected in this study, have been investigated, and they showed tissue-specific pattern. The new variant contains a large deletion in II-III linker that produces a stop codon, which is predicted to produce a two-domain-truncated channel. To study the effect of inflammatory pain on the expression pattern of these variants, animals were treated with intraplantar formalin, and the amount of splice variants in lumbar spinal cord was measured. The results showed that chronic inflammatory pain increases the Ca(v)2.2 mRNA levels lacking exon 18a and decreases the amount of full-length variants, which do not have any deletion. Determining different Ca(v)2.2 splice variants in rat nervous system and the impact of inflammatory pain on the splicing pattern suggest a possible regulatory role for calcium channel alternative splicing.