Somatic and terminal CB1 receptors are differentially coupled to voltage-gated sodium channels in neocortical neurons.
Cell Rep
; 42(3): 112247, 2023 03 28.
Article
em En
| MEDLINE
| ID: mdl-36933217
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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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neocórtex
/
Canais de Sódio Disparados por Voltagem
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos