Depression of neuron responses to acetylcholine by combined application of norepinephrine and substrates of the tricarboxylic acid cycle.
The possible relationship between the function of nicotinic acetylcholine receptors in Lymnaea stagnalis neurons and energy metabolism was studied. Oxidative phosphorylation was activated by treatment of neurons with substrates of the tricarboxylic acid cycle and norepinephrine. Transmembrane currents induced by acetylcholine in isolated neurons were measured by voltage clamp. Succinate dehydrogenase activity was determined histochemically in the same neurons. Cyclic adenosine monophosphate concentration in ganglia were assayed by the protein saturation method of Gilman (1970). When used alone, succinate depressed the responses of about 50% of neurons to acetylcholine. Norepinephrine did not affect the acetylcholine-induced currents but almost doubled the inhibitory action of succinate. The mixture of norepinephrine and isocitrate also diminished the responses to acetylcholine but to a lesser extent than norepinephrine with succinate. A short-term exposure of the ganglia to succinate with norepinephrine led to the activation of succinate dehydrogenase in neurons and a threefold increase in cyclic adenosine monophosphate concentrations in ganglia. When used alone, norepinephrine doubled the cyclic adenosine monophosphate concentration. The results obtained suggest energy-dependent regulation of acetylcholine receptors.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002952:Citric Acid Cycle; D007523:Isocitrates / Q000494:pharmacology; D008195:Lymnaea; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology*; D009712:Nucleotides, Cyclic / Q000378:metabolism; D009994:Osmolar Concentration; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013386:Succinates / Q000494:pharmacology; D019802:Succinic Acid
D007523:Isocitrates; D009712:Nucleotides, Cyclic; D013386:Succinates; C034219:isocitric acid; D019802:Succinic Acid; D013385:Succinate Dehydrogenase; D000109:Acetylcholine; D009638:Norepinephrine