Characterization of beta subunit modulation of a rabbit cardiac L-type Ca2+ channel alpha 1 subunit as expressed in mouse L cells

Abstract

Functional properties of a rabbit cardiac alpha 1 Ca2+ channel subunit (CARD alpha 1) were investigated using the patch-clamp technique in mouse L cells, a recipient cell line which is devoid of any Ca2+ channel subunits. Cell lines resulting from stable transfection of the CARD alpha 1 subunit as well as in coexpression with a beta subunit (CARD alpha 1 beta) derived from skeletal muscle (SKM beta) were characterized. The results show that while the CARD alpha 1-Ca2+ channel activity is negligible, the Ba2+ current density is dramatically increased in the presence of beta subunit (approximately 20-fold). CARD alpha 1- and CARD alpha 1 beta-Ba2+ currents were both sensitive to the 1,4-dihydropyridine (DHP) agonist, Bay K 8644 (5- to 8-fold increase). Activation kinetics of CARD alpha 1- and CARD alpha 1 beta-Ba2+ currents were comparable. The inactivation time-course was faster (3- to 4-fold) for CARD alpha 1 beta-Ba2+ currents. We conclude that the main role of the beta subunit in heart is to modulate the L-type current density and present several lines of evidence that SKM alpha 1 and CARD alpha 1 are differentially regulated by the beta subunit.