Lack of negatively charged residues at the external mouth of Kir2.2 channels enable the voltage-dependent block by external Mg2+
| العنوان: | Lack of negatively charged residues at the external mouth of Kir2.2 channels enable the voltage-dependent block by external Mg2+ |
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| المؤلفون: | Diomedes E. Logothetis, Jun Liu, Hailin Zhang, Yong Zhan, Hui Yu, Junwei Li, Suhua Zhang, Xiao-Xiao Xie, Hailong An |
| المصدر: | PLoS ONE, Vol 9, Iss 10, p e111372 (2014) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Potassium Channels, Xenopus, Biophysics, lcsh:Medicine, Molecular Dynamics Simulation, Inward-Rectifier Potassium Channels, Crystallography, X-Ray, Biochemistry, Ion Channels, Membrane Potentials, Xenopus laevis, Extracellular, Repolarization, Animals, Magnesium, Potassium Channels, Inwardly Rectifying, lcsh:Science, Membrane potential, Ions, Multidisciplinary, Binding Sites, Voltage-gated ion channel, biology, Chemistry, lcsh:R, Biology and Life Sciences, Proteins, biology.organism_classification, Potassium channel, Electrophysiological Phenomena, Electrophysiology, Gene Expression Regulation, Mutation, Oocytes, Potassium, lcsh:Q, Chickens, Ion Channel Gating, Intracellular, Research Article |
| الوصف: | Kir channels display voltage-dependent block by cytosolic cations such as Mg2+ and polyamines that causes inward rectification. In fact, cations can regulate K channel activity from both the extracellular and intracellular sides. Previous studies have provided insight into the up-regulation of Kir channel activity by extracellular K+ concentration. In contrast, extracellular Mg2+ has been found to reduce the amplitude of the single-channel current at milimolar concentrations. However, little is known about the molecular mechanism of Kir channel blockade by external Mg2+ and the relationship between the Mg2+ blockade and activity potentiation by permeant K+ ions. In this study, we applied an interactive approach between theory and experiment. Electrophysiological recordings on Kir2.2 and its mutants were performed by heterologous expression in Xenopus laevis oocytes. Our results confirmed that extracellular Mg2+ could reduce heterologously expressed WT Kir2.2 currents in a voltage dependent manner. The kinetics of inhibition and recovery of Mg2+ exhibit a 3∼4s time constant. Molecular dynamics simulation results revealed a Mg2+ binding site located at the extracellular mouth of Kir2.2 that showed voltage-dependent Mg2+ binding. The mutants, G119D, Q126E and H128D, increased the number of permeant K+ ions and reduced the voltage-dependent blockade of Kir2.2 by extracellular Mg2+. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0741cf10466d955e0c23ec3d05c7d523 http://europepmc.org/articles/PMC4211740?pdf=render |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0741cf10466d955e0c23ec3d05c7d523 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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