1,2-Dioctanoyl-sn-glycerol depresses cardiac L-type Ca2+ current: independent of protein kinase C activation.

ABSTRACT

The present study examines the effect of 1,2-dioctanoyl-sn-glycerol (DiC8), a diacylglycerol analogue, on L-type Ca2+ current (ICa,L) in adult rat ventricular myocytes using whole cell patch-clamp techniques. Extracellular application of DiC8 (1-10 microM) resulted in a concentration-dependent inhibition of peak ICa,L (half-maximum inhibitory concentration = 2.2 microM). Results obtained from the current-voltage relationship showed that DiC8 decreased the slope conductance. In addition, DiC8 increased the rate of Ba2+ current inactivation and caused a hyperpolarizing shift in the steady-state inactivation by 6 mV and a decrease in the slope factor. The DiC8-induced inhibition of ICa,L was neither mimicked by activation of protein kinase C (PKC) with 100 nM phorbol 12-myristate 13-acetate (PMA) no prevented by inhibition of PKC with 30 microM H-7, 100 nM staurosporine, or 24-h pretreatment with PMA. These results suggest that in rat ventricular myocytes 1) 1,2-sn-diacylglycerol (DAG) inhibits ICa,L, possibly by facilitating channel inactivation and decreasing channel availability and 2) this inhibitory effect of DAG is independent of PKC activation.