Synergistic regulation of a neuronal chloride current by intracellular calcium and muscarinic receptor activation: a role for protein kinase C.
Using perforated patch recordings in combination with intracellular Ca2+ ([Ca2+]i) fluorescence measurements, we have identified a delayed Ca(2+)-dependent Cl- current in a mammalian sympathetic ganglion cell. This Cl- current is induced by the synergistic action of Ca2+ and diacylglycerol (DAG) and is blocked by inhibitors of protein kinase C. As a result, the current can be induced by acetylcholine through the conjoint activation of nicotinic receptors (to produce a rise in [Ca2+]i) and muscarinic receptors (to generate DAG). This demonstrates an unusual form of synergism between the two effects of a single transmitter mediated via separate receptors operating within a time scale that could be of physiological significance.
Marsh
S J
SJ
Department of Pharmacology, University College London, England.
Trouslard
J
J
Leaney
J L
JL
Brown
D A
DA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D018118:Chloride Channels / Q000502:physiology*; D004075:Diglycerides / Q000494:pharmacology; D004357:Drug Synergism; D004553:Electric Conductivity; D005728:Ganglia, Sympathetic / Q000166:cytology; D009474:Neurons / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology
D018118:Chloride Channels; D004075:Diglycerides; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D011493:Protein Kinase C; D000109:Acetylcholine; D002118:Calcium