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Updated: Aug 6, 2025

Vibrodissociation of Neurons from Rodent Brain Slices to Study Synaptic Transmission and Image Presynaptic Terminals
Published on: May 25, 2011
Somatic and terminal CB1 receptors are differentially coupled to voltage-gated sodium channels in neocortical neurons
Luke J Steiger1, Timur Tsintsadze1, Glynis B Mattheisen1
1Section of Pulmonary and Critical Care Medicine, VA Portland Health Care System, Portland, OR, USA; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
Abstract:
Endogenous cannabinoid signaling is vital for important brain functions, and the same pathways can be modified pharmacologically to treat pain, epilepsy, and posttraumatic stress disorder. Endocannabinoid-mediated changes to excitability are predominantly attributed to 2-arachidonoylglycerol (2-AG) acting presynaptically via the canonical cannabinoid receptor, CB1. Here, we identify a mechanism in the neocortex by which anandamide (AEA), another major endocannabinoid, but not 2-AG, powerfully inhibits somatically recorded voltage-gated sodium channel (VGSC) currents in the majority of neurons. This pathway involves intracellular CB1 that, when activated by anandamide, decreases the likelihood of recurrent action potential generation. WIN 55,212-2 similarly activates CB1 and inhibits VGSC currents, indicating that this pathway is also positioned to mediate the actions of exogenous cannabinoids on neuronal excitability. The coupling between CB1 and VGSCs is absent at nerve terminals, and 2-AG does not block somatic VGSC currents, indicating functional compartmentalization of the actions of two endocannabinoids.
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