Calcium Channel Ca_Vα₁ Splice Isoforms - Tissue Specificity and Drug Action

Title:Calcium Channel Ca_Vα₁ Splice Isoforms - Tissue Specificity and Drug Action

Volume: 8

Author(s): Diane Lipscombe and Arturo Andrade

Affiliation:

Keywords: Alternative splicing, Cacna1 genes, dihydropyridines, morphine, splicing factors, voltage-gated calcium channels, ziconotide.

Abstract: Voltage-gated calcium ion channels are essential for numerous biological functions of excitable cells and there is wide spread appreciation of their importance as drug targets in the treatment of many disorders including those of cardiovascular and nervous systems. Each Cacna1 gene has the potential to generate a number of structurally, functionally, and in some cases pharmacologically unique Ca_Vα1 subunits through alternative pre-mRNA splicing and the use of alternate promoters. Analyses of rapidly emerging deep sequencing data for a range of human tissue transcriptomes contain information to quantify tissue-specific and alternative exon usage patterns for Cacna1 genes. Cellspecific actions of nuclear DNA and RNA binding proteins control the use of alternate promoters and the selection of alternate exons during pre-mRNA splicing, and they determine the spectrum of protein isoforms expressed within different types of cells. Amino acid compositions within discrete protein domains can differ substantially among Ca_V isoforms expressed in different tissues, and such differences may be greater than those that exist across Ca_V channel homologs of closely related species. Here we highlight examples of Ca_V isoforms that have unique expression patterns and that exhibit different pharmacological sensitivities. Knowledge of expression patterns of Ca_V isoforms in different human tissues, cell populations, ages, and disease states should inform strategies aimed at developing the next generation of Ca_V channel inhibitors and agonists with improved tissue-specificity.

Cite this article as:

Lipscombe Diane and Andrade Arturo, Calcium Channel Ca_Vα₁ Splice Isoforms - Tissue Specificity and Drug Action, Current Molecular Pharmacology 2015; 8 (1) . https://dx.doi.org/10.2174/1874467208666150507103215