New Evidence for Zinc in Synaptic Transmission

4 December 2006

NANCY R GOUGH

In the November 22 issue of Neuron, Hirzel et al. report that mice containing a form of the glycine receptor alpha 1 subunit (GlyRalpha1) that cannot be potentiated by zinc show altered inhibitory neurotransmission. (see the Editors' Choice "Startled by a Lack of Zn2+ (Modulation)", for a summary of the article.)

As zinc targets may include the NMDA and GABA_A receptors, as well as neurotransmitter transporters, these results are intriguing and the technique applied by Hirzel et al. may inspire new ways to investigate the roles of zinc in other types of synaptic activity.

What are the next steps in reconciling these studies with the GlyR that provide strong support for a physiological role for zinc in modulating neurotransmission and the lack of a strong phenotype associated with knocking out the gene encoding vesicular zinc transporter ZnT3?

Where is the zinc that binds the GlyR coming from? Is it tonic modulation or phasic modulation?

As with many important findings, the results of Hirzel et al. lead to more questions and open new avenues of investigation.

K. Hirzel, U. Müller, A. T. Latal, S. Hülsmann, J. Grudzinska, M. W. Seeliger, H. Betz, B. Laube, Hyperekplexia phenotype of glycine receptor α1 subunit mutation mice identifies Zn²⁺ as an essential endogenous modulator of glycinergic neurotransmission. Neuron 52, 679-690 (2006).

A. R. Kay, J. Neyton, P. Paoletti, A startling role for synaptic zinc. Neuron 52, 572-574 (2006).