Auxiliary Ca super(2+) channel subunits: lessons learned from muscle

• Published in: Current opinion in pharmacology 2008-06, Vol.8 (3), p.311-318
• Main Authors: Obermair, G J, Tuluc, P, Flucher, B E
• Format: Article
• Language: English
• ISSN: 1471-4892
• DOI: 10.1016/j.coph.2008.01.008

Voltage-gated Ca super(2+) channels are multi-subunit complexes involved in many key functions of excitable cells. A multitude of studies in heterologous cells demonstrated that coexpression of the pore-forming alpha sub(1) subunits with auxiliary alpha sub(2) delta and beta subunits promotes membrane expression and modulates the biophysical channel properties. New null-mutant animal models and shRNA based knockdown experiments in skeletal muscle cells for the first time demonstrated the physiological roles and possible pathological effects of the alpha sub(2) delta -1 and beta sub(1a) subunits in a differentiated excitable ceil. The alpha sub(2) delta -1 subunit is the determinant of the typical current properties of skeletal and cardiac muscle Ca super(2+) channels. The beta sub(1a) subunit links the skeletal muscle Ca super(2+) channel to the Ca super(2+) release channel in the sarcoplasmic reticulum. Whether these specific functions in muscle indicate similar roles of alpha sub(2) delta and beta subunits as functional modulator and structural organizer, respectively, in neurons is being discussed.