Mediation of acetylcholine's excitatory actions in central neurons

EXS. 1989:57:77-87. doi: 10.1007/978-3-0348-9138-7_8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Acetylcholine / physiology*
  • Animals
  • Carbachol / pharmacology
  • Cyclic GMP / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Isoquinolines / pharmacology
  • Membrane Potentials / drug effects
  • Neurons / drug effects
  • Neurons / physiology*
  • Phorbol Esters / pharmacology
  • Piperazines / pharmacology
  • Protein Kinase C / metabolism
  • Protein Kinase Inhibitors
  • Pyramidal Tracts / drug effects
  • Pyramidal Tracts / physiology*
  • Rats
  • Rats, Inbred Strains
  • Tetrodotoxin / pharmacology

Substances

  • Isoquinolines
  • Phorbol Esters
  • Piperazines
  • Protein Kinase Inhibitors
  • Tetrodotoxin
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide
  • Carbachol
  • Protein Kinase C
  • Cyclic GMP
  • Acetylcholine