Role of cyclic AMP dependent protein kinase in cannabinoid receptor modulation of potassium "A-current" in cultured rat hippocampal neurons

Life Sci. 1995;56(23-24):2081-8. doi: 10.1016/0024-3205(95)00192-9.


Cannabinoid receptor agonists have been previously shown to enhance a potassium A-current (IA) in cultured rat hippocampal neurons. This effect has been further demonstrated to be dependent on G-protein linkage to adenylyl cyclase and levels of intracellular cyclic AMP (cAMP). The present study extends this analysis to the involvement of cAMP-dependent protein kinase (PKA) in this cascade. Specific activators and inhibitors of PKA were shown to have differential effects on the voltage dependence of IA. Specific activators of PKA produced a negative shift in voltage dependence of IA, whereas PKA inhibitors produced a positive shift in IA voltage dependence, the latter similar to that effected by the cannabinoid agonist WIN 55,212-2. Although the negative shift in IA induced by PKA stimulation could be reversed by PKA inhibitors, the positive shift produced by the PKA inhibitors alone was only 50-60% of the cannabinoid-produced shift in IA voltage dependence. This partial effect of PKA inhibition was confirmed by biochemical assays in the same cultured neurons that showed a similar 50-60% decrement in in vitro protein phosphorylation produced by PKA inhibitors. Results are discussed in terms of a diffusible second messenger linkage of the cannabinoid receptor to the A-current channel via the role of protein phosphorylation in modulation of IA.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cannabinoids / metabolism*
  • Cells, Cultured
  • Cyclic AMP / physiology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Hippocampus / cytology
  • Hippocampus / enzymology
  • Hippocampus / physiology*
  • Ion Channel Gating
  • Neurons / enzymology
  • Neurons / physiology*
  • Phosphorylation
  • Potassium Channels / physiology*
  • Rats
  • Receptors, Cannabinoid
  • Receptors, Drug / physiology*


  • Cannabinoids
  • Potassium Channels
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases