Vesicular Zn2+is found at high concentrations in the pre-synapticterminals in the CA3 region of the hippocampus. We demonstratedthat synaptic Zn2+acts via a distinct zinc-sensing receptor (ZnR),GPR39, and triggers metabotropic signaling in CA3 hippocampalneurons. I will describe the role of ZnR signaling in regulating Cl-transport activity mediated by KCC2, the most prominent trans-porter regulating synaptic inhibition. As a result of this process,Zn2+also triggers a pronounced hyperpolarizing shift in the GABAAreversal potential. Using ZnT-3 KO mice, deﬁcient in synaptic Zn2+,or GPR39/ZnR KO mice, we show that the ZnR is an essentialmetabotropic signaling pathway in the CA3. Finally, I will describethe effects of extracellular pH on ZnR signaling and argue that thismay have important implications during disease. Our work eluci-dates a fundamentally important role for synaptically released Zn2+acting as a neurotransmitter signal via the activation of ZnR/GPR39to increase Cl-transport in postsynaptic cells, thereby enhancinginhibitory tone.
|Original language||English GB|
|Number of pages||2|
|Journal||Journal of Neurochemistry|
|State||Published - 2013|