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Biphasic modulation of voltage-dependent currents of retinal cones by cannabinoid CB1 receptor agonist WIN 55212-2

Published online by Cambridge University Press:  26 June 2003

SHIH-FANG FAN
Affiliation:
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook
STEPHEN YAZULLA
Affiliation:
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook

Abstract

Endogenous cannabinoids modulate neurotransmitter action and release in the brain. The effects are exerted on membrane permeability to Ca2+ and K+via protein kinase A (PKA). Cannabinoid CB1 receptors are present at the synaptic terminals of cones in goldfish retina. We investigated the effects of CB1 receptor agonist WIN 55212-2 on voltage-gated currents of goldfish cones. Whole-cell currents were recorded with conventional-patch-clamp methods in goldfish retinal slices. Depolarizing pulses elicited inward ICa and Ioutward that contained several components: IK, IA, and ICl. WIN 55212-2 (<1 μM) enhanced IK, ICl, and ICa, while at >1 μM, IK, ICl, and ICa were suppressed. The voltage-activation ranges of these currents were not affected. All effects of WIN 55212-2 were blocked by the CB1 receptor antagonist SR 141716A as well as the PKA inhibitor Wiptide. The enhancing effect of WIN 55212-2 was blocked selectively by 0.5 nM cholera toxin and the suppressive effect was blocked by pertussis toxin. The results obtained from long and short single cones and double cones were basically the same.

Type
Research Article
Copyright
2003 Cambridge University Press

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