Mediation of acetylcholine's excitatory actions in central neurons.
In experiments on the hippocampus in situ (in rats under urethane), neither cyclic GMP nor H-8 (an antagonist of cyclic nucleotide-dependent kinases) had much effect on CA1/CA3 population spikes or on the excitatory action of ACh. This is further evidence against the idea that cyclic nucleotides play a major role as cholinergic second messengers. On the other hand, the results of tests with a PKC antagonist sphinganine are in keeping with some involvement of PKC in cholinergic actions. (Another PKC antagonist, H-7, proved to be a very powerful excitant, probably via disinhibition). Preliminary experiments on CA1 neurons in hippocampal slices (by single electrode voltage clamp), confirmed previous reports that carbachol depresses A- and C-type K currents, as well as inward Ca2+ currents; though the latter effect was sometimes mainly due to frequency-dependent inactivation of Ca currents. It is suggested that a single, primary muscarinic action, the acceleration of phosphinositide turnover, may account for a variety of secondary effects: on the one hand, via activation of PKC, a number of possible PKC-mediated actions, such as block of the slow AHP; on the other, via IP3 formation, a block of IM and a rise in cycloplasmic free Ca2+ that may cause inactivation of both Ca2(+)-inward currents, and Ca2(+)-dependent GKs.
Agopyan
N
N
Anaesthesia Research Department, McGill University, Montréal, Québec, Canada.
Krnjević
K
K
Leblond
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013779:Tetrodotoxin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D002217:Carbachol; D011493:Protein Kinase C; D006152:Cyclic GMP; D000109:Acetylcholine