Zn2+ ions: modulators of excitatory and inhibitory synaptic activity.
The role of Zn(2+) in the CNS has remained enigmatic for several decades. This divalent cation is accumulated by specific neurons into synaptic vesicles and can be released by stimulation in a Ca(2+)-dependent manner. Using Zn(2+) fluorophores, radiolabeled Zn(2+), and selective chelators, the location of this ion and its release pattern have been established across the brain. Given the distribution and possible release under physiological conditions, Zn(2+) has the potential to act as a modulator of both excitatory and inhibitory neurotransmission. Excitatory N-methyl-D-aspartate (NMDA) receptors are directly inhibited by Zn(2+), whereas non-NMDA receptors appear relatively unaffected. In contrast, inhibitory transmission mediated via GABA(A)receptors can be potentiated via a presynaptic mechanism, influencing transmitter release; however, although some tonic GABAergic inhibition may be suppressed by Zn(2+), most synaptic GABA receptors are unlikely to be modulated directly by this cation. In the spinal cord, glycinergic transmission may also be affected by Zn(2+) causing potentiation. Recently, the penetration of synaptically released Zn(2+) into neurons suggests that this ion has the potential to act as a direct transmitter, by affecting postsynaptic signaling pathways. Taken overall, present studies are broadly supportive of a neuromodulatory role for Zn(2+) at specific excitatory and inhibitory synapses.
Smart
Trevor G
TG
Department of Pharmacology, University College London. t.smart@ucl.ac.uk
Hosie
Alastair M
AM
Miller
Paul S
PS
D000818:Animals; D002413:Cations, Divalent / Q000737:chemistry / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006801:Humans; D009433:Neural Inhibition / Q000502:physiology*; D013569:Synapses / Q000737:chemistry* / Q000378:metabolism*; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
D002413:Cations, Divalent; D015032:Zinc