A protein phosphatase is involved in the cholinergic suppression of the Ca(2+)-activated K(+) current sI(AHP) in hippocampal pyramidal neurons

Neuropharmacology. 2000 Apr 27;39(7):1274-83. doi: 10.1016/s0028-3908(99)00227-0.


The slow calcium-activated potassium current sI(AHP) underlies spike-frequency adaptation and has a substantial impact on the excitability of hippocampal CA1 pyramidal neurons. Among other neuromodulatory substances, sI(AHP) is modulated by acetylcholine acting via muscarinic receptors. The second-messenger systems mediating the suppression of sI(AHP) by muscarinic agonists are largely unknown. Both protein kinase C and A do not seem to be involved, whereas calcium calmodulin kinase II has been shown to take part in the muscarinic action on sI(AHP). We re-examined the mechanism of action of muscarinic agonists on sI(AHP) combining whole-cell recordings with the use of specific inhibitors or activators of putative constituents of the muscarinic pathway. Our results suggest that activation of muscarinic receptors reduces sI(AHP) in a G-protein-mediated and phospholipase C-independent manner. Furthermore, we obtained evidence for the involvement of the cGMP-cGK pathway and of a protein phosphatase in the cholinergic suppression of sI(AHP), whereas release of Ca(2+) from IP(3)-sensitive stores seems to be relevant neither for maintenance nor for modulation of sI(AHP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Carbachol / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic GMP-Dependent Protein Kinases
  • Enzyme Inhibitors / pharmacology
  • Guanylate Cyclase / antagonists & inhibitors
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Muscarinic Agonists / pharmacology
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / enzymology
  • Parasympathetic Nervous System / physiology*
  • Parasympathomimetics / pharmacology
  • Patch-Clamp Techniques
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Kinase Inhibitors
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / enzymology
  • Pyramidal Cells / metabolism*
  • Rats
  • Rats, Wistar
  • Type C Phospholipases / metabolism


  • Enzyme Inhibitors
  • Muscarinic Agonists
  • Parasympathomimetics
  • Protein Kinase Inhibitors
  • Inositol 1,4,5-Trisphosphate
  • Carbachol
  • Cyclic AMP
  • Cyclic GMP-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • Type C Phospholipases
  • Guanylate Cyclase
  • Calcium