Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons

J Neurophysiol. 1997 Jul;78(1):43-50. doi: 10.1152/jn.1997.78.1.43.


Cannabinoids and their analogues have been found to inhibit N- and P/Q-type Ca2+ currents in cell lines and sympathetic neurons transfected with cannabinoid CB1 receptor. However, the effects of cannabinoids on Ca2+ currents in the CNS are largely unexplored. In this study we investigated whether these compounds inhibit Ca2+ channels in cultured rat hippocampal neurons. With the use of antibodies directed against the amino-terminus of the CB1 receptor, we found that in 5-day cultures pyramidally shaped neurons expressed somatic CB1 receptors, whereas in 4-wk cultures the receptor was predominately located on neurites. In early cultures, the cannabimimetic WIN 55,212-2 reversibly inhibited whole cell Ba2+ current in a concentration-dependent (K(1/2) = 21 nM) and pertussis-toxin-sensitive fashion. Inhibition was reduced by the CB1 antagonist SR141716. The current was unaffected by the nonpsychoactive enantiomer WIN 55,212-3. Maximal inhibition by the nonclassical cannabinoid agonist CP 55,940 and by an endogenous cannabinoid, anandamide, were similar to that seen with maximal concentrations of WIN 55,212-2. The Ba2+ current modulated by cannabinoids was carried by N-type (omega-conotoxin-GVIA-sensitive) and P/Q-type (omega-conotoxin-MVIIC-sensitive) channels. These results demonstrate cannabinoid-receptor-mediated inhibition of distinct Ca2+ channels in central neurons. Because the channels that underlie these currents are chiefly located presynaptically, and are required for evoked neurotransmitter release, our results suggest a major role for cannabinoids (endogenous and exogenous) in the modulation of synaptic transmission at CNS synapses.

Publication types

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

MeSH terms

  • Animals
  • Arachidonic Acids / pharmacology
  • Benzoxazines
  • Calcium Channel Blockers / pharmacology*
  • Cannabinoids / pharmacology*
  • Cells, Cultured
  • Cyclohexanols / pharmacology
  • Endocannabinoids
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Membrane Potentials / drug effects
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Picrotoxin / pharmacology
  • Polyunsaturated Alkamides
  • Rats


  • Arachidonic Acids
  • Benzoxazines
  • Calcium Channel Blockers
  • Cannabinoids
  • Cyclohexanols
  • Endocannabinoids
  • Morpholines
  • Naphthalenes
  • Polyunsaturated Alkamides
  • Picrotoxin
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • anandamide