Evidence that Ca/calmodulin-dependent protein kinase mediates the modulation of the Ca2+-dependent K+ current, IAHP, by acetylcholine, but not by glutamate, in hippocampal neurons

Pflugers Arch. 1996 Mar;431(5):723-8.


Muscarinic and metabotropic glutamate receptor agonists increase the excitability of hippocampal and other cortical neurons by suppressing the Ca2+-activated K+current, IAHP, which underlies the slow afterhyperpolarization (AHP) and spike frequency adaptation. We have examined the mechanism of action of a muscarinic agonist (carbachol) and a metabotropic glutamate receptor agonist (1-Aminocyclopentane-trans-1,3-dicarboxylic acid; t-ACPD) on IAHP in hippocampal CA1 neurons in slices, by using highly specific protein kinase inhibitors. We found that inhibition of protein kinase A (PKA) with the adenosine 3',5'-cyclic monophosphate (cAMP) analogue Rp-adenosine-3',5'-cyclic phosphorothioate Rp-cAMPS, did not prevent the muscarinic and glutamatergic suppression of IAHP. In contrast, two specific peptide inhibitors of Ca2+/calmodulin-dependent protein kinase II (CaM-K II), each partially blocked the effect of carbachol, but not the effect of t-ACPD on IAHP. We conclude that CaM-K II, but not PKA, is involved in mediating the muscarinic suppression of IAHP, although other pathways may also contribute. In contrast, neither CaM-K II nor PKA seems to mediate the metabotropic glutamate receptor action on IAHP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology*
  • Amino Acid Sequence
  • Animals
  • Calcium / pharmacology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Carbachol / pharmacology
  • Cricetinae
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Hippocampus / cytology*
  • Molecular Sequence Data
  • Neurons / chemistry*
  • Potassium Channels / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists
  • Signal Transduction


  • Potassium Channels
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Carbachol
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Acetylcholine
  • Calcium