Protein kinase activator 1-oleoyl-2-acetyl-sn-glycerol inhibits two types of calcium currents in GH3 cells.
Two types of Ca2+ currents, high-threshold, long-lasting, or L currents and low-threshold, transient, or T currents, are present in many excitable cells. L-type Ca2+ current is modulated by, among others, beta- and alpha-adrenoreceptors and intracellular Ca2+, but modulation of T-type Ca2+ current is less well established. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a synthetic activator of protein kinase C (PKC), modulates whole cell Ca2+ currents in a variety of excitable cells. Whether activators of PKC affect preferentially L and T types of Ca2+ currents is unknown. We tested OAGs effects on whole cell Ca2+ currents in the clonal GH3 line of anterior pituitary cells. The currents were measured using the whole cell patch-clamp method. Four to 60 microM OAG reversibly reduced Ca2+ currents produced by test potentials to 10 mV, and the inhibition was half maximal at approximately 25 microM. Such concentrations depress Ca2+ currents in chick embryo dorsal root ganglion (DRG) cells and clonal AtT-20 pituitary cells. To test whether OAG acted preferentially on L or T current, we separated the two using depolarizing prepulses to inactivate T current. OAG (40 microM) attenuated T currents by 60% and L currents by 50%. The current waveforms were not changed and were simply scaled, and the effects on both occurred approximately 15 s after OAG was applied. In chick embryo DRGs OAG inhibited the T current by 30% and the L current by 50%. We conclude that PKC modulates Ca2+ currents by acting on both L and T Ca2+ channels.
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D002642:Chick Embryo; D004075:Diglycerides / Q000494:pharmacology*; D004594:Electrophysiology; D004789:Enzyme Activation; D005727:Ganglia, Spinal / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*
D004075:Diglycerides; D005989:Glycerides; D007473:Ion Channels; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D002118:Calcium