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Canna~Fangled Abstracts

Synaptic Zn2+ Inhibits Neurotransmitter Release by Promoting Endocannabinoid Synthesis.

By May 31, 2013No Comments
Pub MedJ Neurosci. 2013 May 29;33(22):9259-9272.

Synaptic Zn2+ Inhibits Neurotransmitter Release by Promoting EndocannabinoidSynthesis.


Departments of Otolaryngology, Pharmacology and Chemical Biology, and Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and Department of Morphology, Ben-Gurion University, Faculty of Health Sciences, Beer-Sheva 84015, Israel.


Although it is well established that many glutamatergic neurons sequester Zn2+ within their synaptic vesicles, the physiological significance of synaptic Zn2+ remains poorly understood. In experiments performed in a Zn2+-enriched auditory brainstem nucleus-the dorsal cochlear nucleus-we discovered that synaptic Zn2+ and GPR39, a putative metabotropic Zn2+-sensing receptor (mZnR), are necessary for triggering the synthesis of theendocannabinoid 2-arachidonoylglycerol (2-AG). The postsynaptic production of 2-AG, in turn, inhibits presynaptic probability of neurotransmitter release, thus shaping synaptic strength and short-term synaptic plasticity. Zn2+-induced inhibition of transmitter release is absent in mutant mice that lack either vesicular Zn2+or the mZnR. Moreover, mass spectrometry measurements of 2-AG levels reveal that Zn2+-mediated initiation of 2-AG synthesis is absent in mice lacking the mZnR. We reveal a previously unknown action of synaptic Zn2+: synaptic Zn2+ inhibits glutamate release by promoting 2-AG synthesis.

[PubMed – as supplied by publisher]

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