Referenced in: none

Automatically associated channels: Kv2.1

Title: Uncoupling charge movement from channel opening in voltage-gated potassium channels by ruthenium complexes.

Authors: Andrés Jara-Oseguera, Itzel G Ishida, Gisela E Rangel-Yescas, Noel Espinosa-Jalapa, José A Pérez-Guzmán, David Elías-Viñas, Ronan Le Lagadec, Tamara Rosenbaum, León D Islas

Journal, date & volume: J. Biol. Chem., 2011 May 6 , 286, 16414-25

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21454671

Abstract
The Kv2.1 channel generates a delayed-rectifier current in neurons and is responsible for modulation of neuronal spike frequency and membrane repolarization in pancreatic β-cells and cardiomyocytes. As with other tetrameric voltage-activated K(+)-channels, it has been proposed that each of the four Kv2.1 voltage-sensing domains activates independently upon depolarization, leading to a final concerted transition that causes channel opening. The mechanism by which voltage-sensor activation is coupled to the gating of the pore is still not understood. Here we show that the carbon-monoxide releasing molecule 2 (CORM-2) is an allosteric inhibitor of the Kv2.1 channel and that its inhibitory properties derive from the CORM-2 ability to largely reduce the voltage dependence of the opening transition, uncoupling voltage-sensor activation from the concerted opening transition. We additionally demonstrate that CORM-2 modulates Shaker K(+)-channels in a similar manner. Our data suggest that the mechanism of inhibition by CORM-2 may be common to voltage-activated channels and that this compound should be a useful tool for understanding the mechanisms of electromechanical coupling.