Inhibition of N- and P/Q-type Ca2+ channels by cannabinoid receptors in single cerebrocortical nerve terminals

FEBS Lett. 2005 Jan 31;579(3):768-72. doi: 10.1016/j.febslet.2004.12.065.


Since cannabinoid receptors inhibit excitatory synaptic transmission by reducing glutamate release, we have examined whether this might occur through the direct inhibition of presynaptic Ca2+ channels. In cerebrocortical nerve terminals, activation of cannabinoid receptors with WIN55,212-2 reduces the KCl-evoked release of glutamate. However, this inhibition is attenuated when N- and P/Q-type Ca2+ channels are blocked. Through Ca2+ imaging in single nerve terminals, we found that WIN55,212-2 reduced the influx of Ca2+ both in nerve terminals that contain N-type Ca2+ channels and those that contain P/Q-type Ca2+ channels. Thus, cannabinoid receptors modulate the two major Ca2+ channels coupled to glutamate release in the cerebral cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines
  • Calcium / metabolism
  • Calcium Channels / physiology*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiology
  • Ion Transport
  • Male
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Nerve Endings / drug effects*
  • Nerve Endings / metabolism
  • Nerve Endings / physiology
  • Rats
  • Rats, Wistar
  • Receptors, Cannabinoid / physiology*


  • Benzoxazines
  • Calcium Channels
  • Morpholines
  • Naphthalenes
  • Receptors, Cannabinoid
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Calcium