Referenced in: none

Automatically associated channels: Kv10.1

Title: An active-site histidine of NR1/2C mediates voltage-independent inhibition by zinc.

Authors: A T Gray, D J Leonoudakis, C S Yost

Journal, date & volume: Brain Res. Mol. Brain Res., 1997 Dec 1 , 52, 157-61

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9450689

Abstract
Endogenous zinc is an important modulator of ion channels of the central nervous system. To understand mechanisms of zinc inhibition, cloned heteromeric N-methyl-D-aspartate receptors (primary subunit NR1 with secondary subunits NR2A, NR2C or NR2D) were expressed in Xenopus oocytes and studied under two-electrode voltage-clamp. Voltage-independent inhibition of NR1/2A heteromers by nanomolar concentrations of extracellular zinc was observed in barium-containing perfusion solutions. In contrast, voltage-independent zinc inhibition of NR1/2C heteromers occurred with lower affinity. Zinc inhibition data from NR1/2D heteromers was fit well with a voltage-independent one-site model and resembled that previously reported for NR1/2B. Reduction of zinc inhibition of NR1/2C heteromers was seen after labeling with the histidine-modifying reagent diethylpyrocarbonate. This finding suggests that the NR1/2C heteromeric ion channel contains an active-site histidine responsible for zinc inhibition.