A diacylglycerol analogue reduces neuronal calcium currents independently of protein kinase C activation.
Diacylglycerol analogues (for example 1,2-oleoylacetylglycerol, OAG) and phorbol esters are activators of protein kinase C, and have been widely used to study the function of this enzyme in both intact cells and cell-free preparations. Electrophysiological studies have shown that these activators can either depress or increase Ca2+ currents, or decrease K+ currents when applied outside the cell. It has been assumed that these effects are mediated by protein kinase C activation. Here we report that micromolar levels of OAG and phorbol esters depress Ca2+ currents in chick sensory neurons independently of their effect as activators of protein kinase C. The depression of the Ca2+ current is rapid and is unaffected by intracellular application of the protein kinase C inhibitors staurosporin, sphingosine and H-7. Furthermore, the activators were ineffective when applied intracellularly, indicating that their site of action is on the outside of the membrane.
Hockberger
P
P
Department of Neurophysiology, Max Planck Institute for Psychiatry, Martinsried-Planegg, FRG.
Toselli
M
M
Swandulla
D
D
Lux
H D
HD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002642:Chick Embryo; D004075:Diglycerides / Q000031:analogs & derivatives* / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000378:metabolism; D005989:Glycerides / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D009474:Neurons / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*
D004075:Diglycerides; D005989:Glycerides; D010703:Phorbol Esters; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D002118:Calcium