1,2-Dioctanoyl-sn-glycerol depresses cardiac L-type Ca2+ current: independent of protein kinase C activation.
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.
Schreur
K D
KD
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Liu
S
S
D000818:Animals; D001464:Barium / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology*; D004553:Electric Conductivity; D004789:Enzyme Activation; D006706:Homeostasis; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016276:Ventricular Function
D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D001464:Barium; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium