PMID: 8972392Dec 1, 1996Paper

A unique role for the S4 segment of domain 4 in the inactivation of sodium channels

The Journal of General Physiology
L Q ChenR G Kallen

Abstract

Sodium channels have four homologous domains (D1-D4) each with six putative transmembrane segments (S1-S6). The highly charged S4 segments in each domain are postulated voltage sensors for gating. We made 15 charge-neutralizing or -reversing substitutions in the first or third basic residues (arginine or lysine) by replacement with histidine, glutamine, or glutamate in S4 segments of each domain of the human heart Na+ channel. Nine of the mutations cause shifts in the conductance-voltage (G-V) midpoints, and all but two significantly decrease the voltage dependence of peak Na+ current, consistent with a role of S4 segments in activation. The decreases in voltage dependence of activation were equivalent to a decrease in apparent gating charge of 0.5-2.1 elementary charges (eo) per channel for single charge-neutralizing mutations. Three charge-reversing mutations gave decreases of 1.2-1.9 eo per channel in voltage dependence of activation. The steady-state inactivation (h infinity) curves were fit by single-component Boltzmann functions and show significant decreases in slope for 9 of the 15 mutants and shifts of midpoints in 9 mutants. The voltage dependence of inactivation time constants is markedly decreased by mutations only ...Continue Reading

Citations

Sep 1, 2005·Pflügers Archiv : European journal of physiology·Alice D LamDorothy A Hanck
Jul 20, 2007·Pflügers Archiv : European journal of physiology·Martina KurejováNorbert Klugbauer
Dec 8, 2006·Cellular and Molecular Neurobiology·James R GroomeDavid Petty
Apr 26, 2002·Trends in Neurosciences·Sulayman Dib-HajjStephen G Waxman
May 9, 2006·The Journal of Biological Chemistry·Sandrine CestèleWilliam A Catterall
Oct 6, 1997·The Journal of General Physiology·K J Kontis, A L Goldin
Apr 18, 1998·The Journal of General Physiology·N MitrovicR Horn
Apr 25, 2000·The Journal of General Physiology·M F SheetsD A Hanck
Jun 1, 2000·The Journal of General Physiology·N MitrovicR Horn
Aug 30, 2000·The Journal of General Physiology·R HornH J Gruber
Feb 5, 2003·The Journal of General Physiology·Michael F Sheets, Dorothy A Hanck
Oct 31, 2002·The Journal of General Physiology·Baron Chanda, Francisco Bezanilla
Feb 26, 2004·The Journal of General Physiology·Baron ChandaFrancisco Bezanilla
Dec 29, 2005·The Journal of General Physiology·Carlos G VanoyeAlfred L George
Dec 18, 2008·The Journal of General Physiology·Yukiko Muroi, Baron Chanda
Apr 17, 2013·The Journal of General Physiology·James R Groome, Vern Winston
Jul 17, 2013·The Journal of General Physiology·Deborah L CapesBaron Chanda
Aug 28, 2013·The Journal of General Physiology·Tamer M Gamal El-DinWilliam A Catterall
Jul 17, 2013·The Journal of General Physiology·Christopher A Ahern
Jan 1, 1997·British Journal of Rheumatology·I Butrimiene, A Venalis
Apr 2, 1998·Proceedings. Biological Sciences·R D Keynes, F Elinder
May 27, 1999·Proceedings. Biological Sciences·R D Keynes, F Elinder
Mar 24, 2012·Journal of Neurophysiology·Pin LiuBruce P Bean
Dec 30, 2011·Journal of Neurophysiology·Viktor YarotskyyKeith S Elmslie
Jul 5, 2008·Circulation Research·Hector M Barajas-MartínezRobert Dumaine
Apr 20, 2000·The Journal of Clinical Investigation·N G KambourisJ R Balser
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·N J LinfordW A Catterall
Jan 24, 2016·Journal of Molecular and Cellular Cardiology·Hong-Gang WangGeoffrey S Pitt
Jan 19, 2016·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Koshi KinoshitaNaoki Nishida
Dec 4, 2004·The Journal of Physiology·Michael F Sheets, Dorothy A Hanck
Dec 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Antonios PantazisRiccardo Olcese
Jun 20, 1998·The Journal of Physiology·E MarbanG F Tomaselli

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