Antisense oligonucleotide against the Ca channel β subunit decreases L-type Ca current in rat ventricular myocytes

The role of endogenous β subunits of the L-type Ca channel in native cardiac ventricular myocytes is unclear. We have therefore investigated the effect of inhibiting β subunit expression in rat myocytes, by culturing isolated myocytes for 24 h with either antisense oligonucleotide against the β subunit or with scrambled oligonucleotide (control). α1 subunit expression and distribution were then determined by immunolabeling, and L-type Ca current measured using the whole cell patch–clamp technique. Cells treated with antisense showed increased perinuclear staining for α1, decreased Ca current amplitude and a small rightward shift of the activation curve and the I–V relation, with no significant effect on inactivation. These data suggest that endogenous β subunits in native cardiac myocytes help to traffic the α1 subunit to the cell membrane and thus play a major role in determining Ca current amplitude.