Cannabinoids Inhibit N- and P/Q-Type Calcium Channels in Cultured Rat Hippocampal Neurons

Cannabinoids Inhibit N- and P/Q-Type Calcium Channels in Cultured Rat Hippocampal Neurons Abstract Twitchell, W., S. Brown, and K. Mackie. Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J. Neurophysiol. 78: 43–50, 1997. Cannabinoids and their analogues have been found to inhibit N- and P/Q-type Ca 2+ currents in cell lines and sympathetic neurons transfected with cannabinoid CB1 receptor. However, the effects of cannabinoids on Ca 2+ currents in the CNS are largely unexplored. In this study we investigated whether these compounds inhibit Ca 2+ 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 predomintely located on neurites. In early cultures, the cannabimimetic WIN 55,212-2 reversibly inhibited whole cell Ba 2+ 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 Ba 2+ current modulated by cannabinoids was carried by N-type (ω-conotoxin-GVIA-sensitive) and P/Q-type (ω-conotoxin-MVIIC-sensitive) channels. These results demonstrate cannabinoid-receptor-mediated inhibition of distinct Ca 2+ 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. Footnotes Address for reprint requests: K. Mackie, Dept. of Anesthesiology, Box 356540, University of Washington, Seattle, WA 98195-6540. Copyright © 1997 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurophysiology The American Physiological Society

Cannabinoids Inhibit N- and P/Q-Type Calcium Channels in Cultured Rat Hippocampal Neurons

Journal of Neurophysiology, Volume 78 (1): 43 – Jul 1, 1997

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0022-3077
eISSN
1522-1598
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Abstract

Abstract Twitchell, W., S. Brown, and K. Mackie. Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J. Neurophysiol. 78: 43–50, 1997. Cannabinoids and their analogues have been found to inhibit N- and P/Q-type Ca 2+ currents in cell lines and sympathetic neurons transfected with cannabinoid CB1 receptor. However, the effects of cannabinoids on Ca 2+ currents in the CNS are largely unexplored. In this study we investigated whether these compounds inhibit Ca 2+ 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 predomintely located on neurites. In early cultures, the cannabimimetic WIN 55,212-2 reversibly inhibited whole cell Ba 2+ 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 Ba 2+ current modulated by cannabinoids was carried by N-type (ω-conotoxin-GVIA-sensitive) and P/Q-type (ω-conotoxin-MVIIC-sensitive) channels. These results demonstrate cannabinoid-receptor-mediated inhibition of distinct Ca 2+ 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. Footnotes Address for reprint requests: K. Mackie, Dept. of Anesthesiology, Box 356540, University of Washington, Seattle, WA 98195-6540. Copyright © 1997 the American Physiological Society

Journal

Journal of NeurophysiologyThe American Physiological Society

Published: Jul 1, 1997

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