title: Uncoupling charge movement from channel opening in voltage-gated potassium channels by ruthenium complexes.
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.
authors: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Distrito Federal, México.
authors: Andrés
authors: A
authors: Jara-Oseguera
authors: Itzel G
authors: IG
authors: Ishida
authors: Gisela E
authors: GE
authors: Rangel-Yescas
authors: Noel
authors: N
authors: Espinosa-Jalapa
authors: José A
authors: JA
authors: Pérez-Guzmán
authors: David
authors: D
authors: Elías-Viñas
authors: Ronan
authors: R
authors: Le Lagadec
authors: Tamara
authors: T
authors: Rosenbaum
authors: León D
authors: LD
authors: Islas
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D050417:Insulin-Secreting Cells / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D051381:Rats; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051637:Shaker Superfamily of Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: C496991:Kcnb1 protein, rat; D009942:Organometallic Compounds; D026902:Potassium Channel Blockers; D051669:Shab Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; C447082:tricarbonyldichlororuthenium (II) dimer