The cannabinoid agonist Win55,212-2 inhibits calcium channels by receptor-mediated and direct pathways in cultured rat hippocampal neurons

Maoxing Shen, Stanley A Thayer

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

The effects of the cannabinoid receptor agonist Win55,212 on Ca2+ channels were studied in rat hippocampal neurons grown in primary culture. Win55,212-2 inhibited whole-cell Ba2+ currents through Ca2+ channels by both CB1 receptor-mediated and direct mechanisms. The concentration dependent inhibition of the current showed two clear phases, a high-affinity receptor- mediated phase (IC50 = 14 ± 2 nM) that was stereoselective and sensitive to a CB1 receptor antagonist, 300 nM SR141716, and a non-saturating phase that was neither stereoselective nor inhibited by SR141716. These concentration-dependent effects were paralleled by Win55212-induced inhibition of glutamatergic synaptic transmission. Win55,212-2 (100 nM) inhibited both ω-agatoxin IVA- and ω-conotoxin GVIA-sensitive currents. Thus, activation of cannabinoid receptors inhibits N- and P/Q-type Ca2+ channels. Activation of cannabinoid receptors inhibited only a fraction of the whole-cell Ca2+ channel current (17 ± 2%) even though more than half of the whole-cell Ba2+ current was carried by N- and P/Q-type Ca2+ channels. Concentrations of agonist greater than 1 μM inhibited Ca2+ channels directly.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalBrain Research
Volume783
Issue number1
DOIs
StatePublished - Feb 2 1998

Keywords

  • Calcium channel
  • Cannabinoid
  • Hippocampus
  • Patch-clamp

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