Mathie, Alistair and Sutton, Gemma L. and Clarke, Catherine E. and Veale, Emma L. (2006) Zinc and copper: pharmacological probes and endogenous modulators of neuronal excitability. Pharmacology & Therapeutics, 111 (3). pp. 567-583. ISSN 0163-7258. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)
As well as being key structural components of many proteins, increasing evidence suggests that zinc and copper ions function as signaling molecules in the nervous system and are released from the synaptic terminals of certain neurons. In this review, we consider the actions of these two ions on proteins that regulate neuronal excitability. In addition to the established actions of zinc, and to a lesser degree copper, on excitatory and inhibitory ligand-gated ion channels, we show that both ions have a number of actions on selected members of the voltage-gated-like ion channel superfamily. For example, zinc is a much more effective blocker of one subtype of tetrodotoxin (TTX)-insensitive sodium (Na+) channel (NaV1.5) than other Na+ channels, whereas a certain T-type calcium (Ca2+) channel subunit (CaV3.2) is particularly sensitive to zinc. For potassium (K+) channels, zinc can have profound effects on the gating of certain KV channels whereas zinc and copper have distinct actions on closely related members of the 2 pore domain potassium channel (K2P) channel family. In addition to direct actions on these proteins, zinc is able to permeate a number of membrane proteins such as (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptors, Ca2+ channels and some transient receptor potential (trp) channels. There are a number of important physiological and pathophysiological consequences of these many actions of zinc and copper on membrane proteins, in terms of regulation of neuronal excitability and neurotoxicity. Furthermore, the concentration of free zinc and copper either in the synaptic cleft or neuronal cytoplasm may contribute to the etiology of certain disease states such as Alzheimer's disease (AD) and epilepsy.
|Subjects:||Q Science > QP Physiology (Living systems)|
|Divisions:||Faculties > Science Technology and Medical Studies > Medway School of Pharmacy|
|Depositing User:||Alistair Mathie|
|Date Deposited:||16 Mar 2009 08:59|
|Last Modified:||25 Jun 2014 09:48|
|Resource URI:||https://kar.kent.ac.uk/id/eprint/5627 (The current URI for this page, for reference purposes)|