Research Alert
Newswise — Rockville, Md. (January 8, 2023)—A new study of a key gene may hold the answer to developing new drugs to treat chronic pain. Physiologists initially set out to investigate the functional importance of the short versus long versions of exon 47 present in the C-terminus of the N-type calcium channel. An exon is a subset of a gene within the mRNA molecule. This channel is important because it’s the first synapse in the pain pathway of the spinal cord.
The two-part findings are published in the journal Function. Researchers first discovered that in the available sequence databases, short exon 47 was only present in channel sequences that did not contain another exon 18a. Next, they found long exon 47, only in the additional presence of exon 18a, resulted in much larger N-type channel currents than the other three combinations. By comparison, cell surface expression of the channel was increased by long exon 47 as opposed to short exon 47, regardless of whether exon 18a is present. As a result, the additional presence of exon 18a must affect channel function at the level of increasing its ability to open, rather than by enhancing the amount of channel on the cell surface. “Our study highlights the importance of investigating the combinatorial effects of exon inclusion, rather than each in isolation, to increase our understanding of calcium channel function, and for future drug discovery,” said Annette Dolphin, PhD, of University College London and the study’s lead author.
Read the full article, “The interplay between splicing of two exon combinations differentially affects membrane targeting and function of human CaV2.2,” published ahead of print in Function. Contact APS Media Relations or call 301.634.7314 to schedule an interview with a member of the research team.
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