Evidence exists that cannabinoid receptor type 1 can inhibit voltage-gated calcium channel, decrease intracellular Ca2+ influx, and reduce neurotransmitter release. However, some scholars demonstrated that cannabinoid receptor type 1 can increase extracellular Ca2+ influx and increase neurotransmitter release.

Dr. Yi Zhang and his team, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, China used whole cell voltage-clamp and calcium imaging in cultured trigeminal ganglion neurons and found that anandamide directly caused Ca2+ influx, which then triggered an increase of intracellular Ca2+ concentration. Inhibition of voltage-gated calcium channel by anandamide and increase in intracellular Ca2+ concentration by anandamide are two independent events.

The underlying mechanisms are similar, both are bidirectional. That is to say, low concentration of anandamide exerts effects by activating cannabinoid receptor type 1 and high concentration of anandamide exerts effects by activating cannabinoid receptor type 1 and vanilloid receptor type 1.

The signaling pathways involved in two independent events are different. Protein kinase C signaling pathway is involved in anandamide inhibition of voltage-gated calcium channel, but it does not participate in the process during which anandamide increases intracellular Ca2+ concentration.

These findings provide evidence for studying the mechanism underlying the neural excitatory effects of anandamide. Related results were published in Neural Regeneration Research (Vol. 9, No. 8, 2014).

Article: " Regulatory effects of anandamide on intracellular Ca2+ concentration increase in trigeminal ganglion neurons," by Yi Zhang1, Hong Xie2, Gang Lei3, Fen Li3, Jianping Pan3, Changjin Liu3, Zhiguo Liu4, Lieju Liu4, Xuehong Cao3, 4 (1 Department of Anesthesiology, Tongji Hospital Affliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; 2 Jingzhou Central Hospital, Jingzhou, Hubei Province, China; 3 Department of Physiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China; 4 Department of Bioengineering, Wuhan Institute of Engineering, Wuhan, Hubei Province, China)

ZhangY, Xie H, Lei G, Li F, Pan JP, Liu CJ, Liu ZG, Liu LJ, Cao XH. Regulatory effects of anandamide on intracellular Ca2+ concentration increase in trigeminal ganglion neurons. Neural Regen Res. 2014;9(8):878-887.