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Cannabinoids, TRPV and nitric oxide: the three ring circus of neuronal excitability

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A Correction to this article was published on 11 December 2019

This article has been updated

Abstract

Endocannabinoid system is considered a relevant player in the regulation of neuronal excitability, since it contributes to maintaining the balance of the synaptic ionic milieu. Perturbations to bioelectric conductances have been implicated in the pathophysiological processes leading to hyperexcitability and epileptic seizures. Cannabinoid influence on neurosignalling is exerted on classic receptor-mediated mechanisms or on further molecular targets. Among these, transient receptor potential vanilloid (TRPV) are ionic channels modulated by cannabinoids that are involved in the transduction of a plethora of stimuli and trigger fundamental downstream pathways in the post-synaptic site. In this review, we aim at providing a brief summary of the most recent data about the cross-talk between cannabinoid system and TRPV channels, drawing attention on their role on neuronal hyperexcitability. Then, we aim to unveil a plausible point of interaction between these neural signalling systems taking into consideration nitric oxide, a gaseous molecule inducing profound modifications to neural performances. From this novel perspective, we struggle to propose innovative cellular mechanisms in the regulation of hyperexcitability phenomena, with the goal of exploring plausible CB-related mechanisms underpinning epileptic seizures.

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Change history

  • 11 December 2019

    In the original publication of the article, the names of the authors were incorrectly swapped as Gambino Giuditta · Rizzo Valerio · Giglia Giuseppe · Ferraro Giuseppe · Sardo Pierangelo.

Abbreviations

2AG:

2-Arachidonoylglycerol

7NI:

7-Nitroindazole

ACEA:

2′-Chloroethylamide

AEA:

Anandamide

CA1:

Cornus ammonis 1

CA3:

Cornus ammonis 3

cAMP/PKA:

Cyclic adenosine monophosphate/protein kinase A

CAP:

Capsaicin

CB:

Cannabinoid

CB1R:

Cannabinoid receptor type 1

CB2R:

Cannabinoid receptors type 2

CCK:

Cholecystokinin

cGMP:

Cyclic guanosine monophosphate

CNG:

Cyclic nucleotide-gated

CNS:

Central nervous system

CPZ:

Capsazepine

DGLα:

Diacylglycerol lipase α

DSE:

Depolarization-induced suppression of excitation

DSI:

Depolarization-induced suppression of inhibition

eCB:

Endocannabinoids

EPSCs:

Excitatory post-synaptic currents

FAAH:

Fatty acid amide hydrolase enzyme

GLU:

Glutamate

LTD:

Long-term depression

LTP:

Long-term potentiation

MDA:

Maximal dentate gyrus activation

l-NAME:

N-ω-nitro-l-arginine methyl ester

NO:

Nitric oxide

NOS:

NO synthase

nNOS:

Neuronal NOS

eNOS:

Endothelial NOS

iNOS:

Inducible NOS

PKG:

CGMP-dependent protein kinases

sGC:

Soluble guanylyl cyclase

TLE:

Temporal lobe epilepsy

TRPV1:

Transient receptor potential vanilloid type 1

VGCCs:

Voltage-gated Ca2+ channels

WIN:

(R)-(+)WIN 55,212-2

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  1. Department of Experimental Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Sezione di Fisiologia Umana G. Pagano, University of Palermo, Corso Tukory 129, Palermo, Italy

    Giuditta Gambino, Valerio Rizzo, Giuseppe Giglia, Giuseppe Ferraro & Pierangelo Sardo

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Gambino, G., Rizzo, V., Giglia, G. et al. Cannabinoids, TRPV and nitric oxide: the three ring circus of neuronal excitability. Brain Struct Funct 225, 1–15 (2020). https://doi.org/10.1007/s00429-019-01992-9

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