Faculty Collaboration Database

Cannabinoid receptor agonists inhibit depolarization-induced calcium influx in cerebellar granule neurons. J Neurochem 2001 Oct;79(2):371-81

Date

10/26/2001

Pubmed ID

11677265

DOI

10.1046/j.1471-4159.2001.00567.x

Scopus ID

2-s2.0-0034775812 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

Neuronal cannabinoid receptors (CB(1)) are coupled to inhibition of voltage-sensitive Ca(2+) channels (VSCCs) in several cell types. The purpose of these studies was to characterize the interaction between endogenous CB(1) receptors and VSCCs in cerebellar granule neurons (CGN). Ca(2+) transients were evoked by KCl-induced depolarization and imaged using fura-2. The CB(1) receptor agonists CP55940, Win 55212-2 and N-arachidonylethanolamine (anandamide) produced concentration-related decreases in peak amplitude of the Ca(2+) response and total Ca(2+) influx. Pre-treatment of CGN with pertussis toxin abolished agonist-mediated inhibition. The inhibitory effect of Win 55212-2 on Ca(2+) influx was additive with inhibition produced by omega-agatoxin IVA and nifedipine but not with omega-conotoxin GVIA, indicating that N-type VSCCs are the primary effector. Paradoxically, the CB(1) receptor antagonist, SR141716, also inhibited KCl-induced Ca(2+) influx into CGN in a concentration-related manner. SR141716 inhibition was pertussis toxin-insensitive and was not additive with the inhibition produced by Win 55212-2. Confocal imaging of CGN in primary culture demonstrate a high density of CB(1) receptor expression on CGN plasma membranes, including the neuritic processes. These data demonstrate that the CB(1) receptor is highly expressed by CGN and agonists serve as potent and efficacious inhibitory modulators of Ca(2+) influx through N-type VSCC.

Author List

Nogueron MI, Porgilsson B, Schneider WE, Stucky CL, Hillard CJ

Authors

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acids
Benzoxazines
Calcium
Calcium Channel Blockers
Calcium Channels
Cells, Cultured
Cerebellum
Electrophysiology
Endocannabinoids
Female
Male
Morpholines
Naphthalenes
Neurons
Polyunsaturated Alkamides
Rats
Receptors, Cannabinoid
Receptors, Drug