Uncoupling charge movement from channel opening in voltage-gated potassium channels by ruthenium complexes |
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Authors: | Jara-Oseguera Andrés 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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Institution: | Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Distrito Federal, México. |
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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. |
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Keywords: | Ion Channels Membrane Biophysics Neurobiology Neuroscience Potassium Channels Channel Gating Electromechanical Coupling Voltage Dependence |
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