Regulation of the Activity of Regenerating Motor Synapses Involving Endocannabinoids

The paper reports the study of the effects of the endocannabinoids arachidonoylethanolamide (AEA), also known as anandamide, and 2-arachidonoylglycerol (2-AG) on the parameters of miniature endplate potentials (MEPPs) and evoked endplate potentials (EEPs) of the motor synapses recovering during reinnervation of the mouse extensor digitorum longus muscle. 2-AG increased the amplitude of MEPP by 35% and the amplitude of EPP by 37%, without affecting the quantal content of EPP and other parameters of mediator secretion. The effect was prevented by the vesicular acetylcholine transporter inhibitor vesamicol and the inverse agonist of CB1-type cannabinoid receptor AM251. AEA did not induce changes in the amplitude and other parameters of MEPP but reduced the quantal content of EPP by 27%. The inhibitory effect of AEA was prevented by AM251 as well as by the L-type Ca²⁺ channel blocker nitrendipine. It was demonstrated for the first time that, in regenerating motor synapses, AEA and 2-AG—although activating the same type of presynaptic CB receptors—have different final targets, affect different parameters of quantal acetylcholine secretion, and have opposite effects on synaptic transmission. The presence of both facilitatory and inhibitory effects of endocannabinoids may serve to fine-tune and regulate synaptic transmission during maturation of motor contacts.