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PMID: 21454671 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of biological chemistry ·Vol. 286 ·No. 18 ·2011-05-06 ·Pages 16414-25

Jara-Oseguera A, Ishida IG, Rangel-Yescas GE, Espinosa-Jalapa N, Pérez-Guzmán JA, Elías-Viñas D, Le Lagadec R, Rosenbaum T, Islas LD

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.

MeSH Terms
Allosteric Regulation/drug effects,physiology Animals Insulin-Secreting Cells/metabolism Ion Channel Gating/drug effects,physiology Membrane Potentials/drug effects Organometallic Compounds/pharmacology Potassium Channel Blockers/pharmacology Protein Structure, Tertiary Rats Shab Potassium Channels/antagonists & inhibitors,genetics,metabolism Shaker Superfamily of Potassium Channels/antagonists & inhibitors,genetics,metabolism Xenopus laevis
Chemicals
Kcnb1 protein, rat Organometallic Compounds Potassium Channel Blockers Shab Potassium Channels Shaker Superfamily of Potassium Channels tricarbonyldichlororuthenium (II) dimer
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Jara-Oseguera Andrés
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Distrito Federal, México.
Ishida Itzel G
Rangel-Yescas Gisela E
Espinosa-Jalapa Noel
Pérez-Guzmán José A
Elías-Viñas David
Le Lagadec Ronan
Rosenbaum Tamara
Islas León D
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M110.198010
Published
2011-05-06
Epub
2011-00-17
Pages
16414-25
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3091247
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M110.198010 PMC Full Text View journal details
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