Pharmacological evidence that protein kinase C modulates monosynaptic excitations in the olfactory cortex.
The possible occurrence and role of protein kinase C at the lateral olfactory tract (LOT)-pyramidal cell synapse of the rat olfactory cortex slice has been investigated by determining the effects of both activators (4-beta-phorbol-12,13,diacetate [PDAc] and 1,2-dioctanoyl-sn-glycerol) and inhibitors (5-isoquinolinylsulphonyl)-2-methylpiperazine [H-7], sangivamycin and polymyxin B) of the enzyme on the surface field potential known as the N-wave. PDAc (0.3 to 20 mumol/l) and 1,2-dioctanoyl-sn-glycerol (25 to 250 mumol/l) increased the area and amplitude of the potential. In control slices in which a population spike was recorded, PDAc also triggered the appearance of multiple spikes. In a series of input-output experiments, PDAc (2.5 or 5 mumol/l) increased the area and amplitude of the N-wave relative to that of the action potential but did not significantly affect pyramidal cell excitability. The effects of PDAc on the N-wave were antagonised by all three protein kinase C inhibitors but not by the calmodulin antagonist calmidazolium and were greater in slices perfused with solution containing 10 rather than 1 mmol/l Mg2+ or 1.25 rather than 5 mmol/l Ca2+. The effect of PDAc on the amplitude but not area of the N-wave was blocked by the potassium channel blocker tetraethylammonium (10 mmol/l) but not by 4-aminopyridine (0.25 mmol/l). In a series of conditioning experiments, PDAc (1 to 5 mumol/l) reduced the amplitude of the N-wave evoked by a second stimulus compared to that evoked by the first conditioning pulse.(ABSTRACT TRUNCATED AT 250 WORDS)
Collins
G G
GG
Department of Pharmacology and Therapeutics, Royal Hallamshire Hospital, Sheffield, UK.
Richards
W J
WJ
D000200:Action Potentials / Q000187:drug effects; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009830:Olfactory Bulb / Q000201:enzymology / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011712:Pyramidal Tracts / Q000201:enzymology / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology; D012023:Reflex, Monosynaptic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D000596:Amino Acids; D010703:Phorbol Esters; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C008874:phorbol-12,13-diacetate; D011493:Protein Kinase C; D008274:Magnesium; D002118:Calcium