Regulatory effects of anandamide on intracellular Ca ²⁺ concentration increase in trigeminal ganglion neurons

Abstract

Activation of cannabinoid receptor type 1 on presynaptic neurons is postulated to suppress neurotransmission by decreasing Ca2+ influx through high voltage-gated Ca2+ channels. However, recent studies suggest that cannabinoids which activate cannabinoid receptor type 1 can increase neurotransmitter release by enhancing Ca2+ influx in vitro. The aim of the present study was to investigate the modulation of intracellular Ca2+ concentration by the cannabinoid receptor type 1 agonist anandamide, and its underlying mechanisms. Using whole cell voltage-clamp and calcium imaging in cultured trigeminal ganglion neurons, we found that anandamide directly caused Ca2+ influx in a dose-dependent manner, which then triggered an increase of intracellular Ca2+ concentration. The cyclic adenosine and guanosine monophosphate-dependent protein kinase systems, but not the protein kinase C system, were involved in the increased intracellular Ca2+ concentration by anandamide. This result showed that anandamide increased intracellular Ca2+ concentration and inhibited high voltage-gated Ca2+ channels through different signal transduction pathways.

Alcohol Versus Cannabinoids: A Review of their Opposite Neuro-Immunomodulatory Effects and Future Therapeutic Potentials

“…Recent studies suggest that cannabinoids, including endocannabinoids, which activate CB 1 can increase neurotransmitter release by enhancing Ca(2+) influx in vitro; which demonstrates a crucial role of endocannabinoid -induced potentiation of neurotransmission [75]. Moreover, enhancement of endocannabinoid signaling can serve as a neuro-protective therapeutic modality by activating signaling pathways downstream from cannabinoid receptors, eventually promoting neuronal maintenance and function, and also subsequently supporting the endocannabinoid system as a target for novel therapeutic drugs [76,77].…”

Receptor-Dependent and Independent Regulation of Voltage-Gated Ca2+ Channels and Ca2+-Permeable Channels by Endocannabinoids in the Brain

“…L-type channels form the largest family of the VGCCs and, due to the specific expression pattern in the brain, they play a significant physiological role in diverse cellular processes including neuronal development, regulation of cell cycle, neurotransmission or gene expression. A number of studies have shown that activity of L-type of VGCCs can be regulated by eCBs, mainly by the CB1R [ 100 , 101 ]. Electrophysiological and pharmacological data showed that activation of dendritic L-type Ca 2+ channels and the subsequent release of 2-AG acting on the presynaptic CB1 receptors triggered retrograde short-term depression (STD) in bed nucleus of the stria terminalis (BNST) neurons and in spiny neurons in corticostriatal slices [ 102 ].…”

Gap Junction Blockers: An Overview of their Effects on Induced Seizures in Animal Models

“…ANA and OLE are members of the cannabinoid family and these endogenous molecules bind and activate the cannabinoid receptor 1 [ 86 ]. Some reports have demonstrated that these endocannabinoids have effects on Ca+ channels and significantly increase the intracellular concentration of Ca 2+ in different cell types [ 87 , 88 ]. Interestingly, it has been described that both, ANA and OLE, are potent inhibitors of intercellular gap junctional communication in glial cells, and ANA also blocked calcium wave propagation in striatal astrocytes [ 89 , 90 ].…”