title: Identification of a key residue in Kv7.1 potassium channel essential for sensing external potassium ions.
abstract: Kv7.1 voltage-gated K(+) (Kv) channels are present in the apical membranes of marginal cells of the stria vascularis of the inner ear, where they mediate K(+) efflux into the scala media (cochlear duct) of the cochlea. As such, they are exposed to the K(+)-rich (∼ 150 mM of external K(+) (K(+) e)) environment of the endolymph. Previous studies have shown that Kv7.1 currents are substantially suppressed by high K(+) e (independent of the effects of altering the electrochemical gradient). However, the molecular basis for this inhibition, which is believed to involve stabilization of an inactivated state, remains unclear. Using sequence alignment of S5-pore linkers of several Kv channels, we identified a key residue, E290, found in only a few Kv channels including Kv7.1. We used substituted cysteine accessibility methods and patch-clamp analysis to provide evidence that the ability of Kv7.1 to sense K(+) e depends on E290, and that the charge at this position is essential for Kv7.1's K(+) e sensitivity. We propose that Kv7.1 may use this feedback mechanism to maintain the magnitude of the endocochlear potential, which boosts the driving force to generate the receptor potential of hair cells. The implications of our findings transcend the auditory system; mutations at this position also result in long QT syndrome in the heart.
authors.affiliation: Department of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557.
authors.forename: Wenying
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557.
authors.forename: Maria Cristina Perez
authors.initials: MC
authors.lastname: Flores
authors.affiliation: Department of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557.
authors.forename: Choong-Ryoul
authors.initials: CR
authors.lastname: Sihn
authors.affiliation: Department of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California, Davis, Davis, CA 95616.
authors.forename: Yinuo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Doyle
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California, Davis, Davis, CA 95616 Department of Veterans Affairs, Northern California Health Care System, Mather, CA 95655.
authors.forename: Nipavan
authors.initials: N
authors.lastname: Chiamvimonvat
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California, Davis, Davis, CA 95616 enyamoah@gmail.com xdzhang@ucdavis.edu.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: Department of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557 enyamoah@gmail.com xdzhang@ucdavis.edu.
authors.forename: Ebenezer N
authors.initials: EN
authors.lastname: Yamoah
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D018698:Glutamic Acid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism*
chemical_list: D051657:KCNQ1 Potassium Channel; D018698:Glutamic Acid; D011188:Potassium