caa a22 4500 46325404X CHVBK 20180405153349.0 cr unu---uuuuu 170326e20070101xx s 000 0 eng 10.1007/s10571-006-9120-2 doi (NATIONALLICENCE)springer-10.1007/s10571-006-9120-2 Central Charged Residues in DIIIS4 Regulate Deactivation Gating in Skeletal Muscle Sodium Channels [Elektronische Daten] [James Groome, Heidi Alexander, Esther Fujimoto, Megan Sherry, David Petty] Summary: 1. Mutations in the S4 segment of domain III in the voltage gated skeletal muscle sodium channel hNaV1.4 were constructed to test the roles of each charged residue in deactivation gating. Mutations comprised charge reversals at K1-R6, charge neutralization, and substitution at R4 and R5. 2. Charge-reversing mutations at R4 and R5 produced the greatest alteration of activation parameters compared to hNaV1.4. Effects included depolarization of the conductance/voltage (g/V) curve, decreased valence and slowing of kinetics. 3. Reversal of charge at R2 to R4 hyperpolarized, and reversal at R5 or R6 depolarized the h ∞ curve. Most DIIIS4 mutations slowed inactivation from the open state. R4E slowed closed state fast inactivation and R5E inhibited its completion. 4. Deactivation from the open and/or inactivated state was prolonged in mutations reversing charge at R2 to R4 but accelerated by reversal of charge at R5 or R6. Effects were most pronounced at central charges R4 and R5. 5. Charge and structure each contribute to effects of mutations at R4 and R5 on channel gating. Effects of mutations on activation and deactivation at R4 and, to a lesser extent R5, were primarily owing to charge alteration, whereas effects on fast inactivation were charge independent. Springer Science+Business Media, LLC, 2006 sodium channel nationallicence voltage sensor nationallicence deactivation nationallicence Groome James Department of Biological Sciences, Idaho State University, 83204, Pocatello, ID, USA aut Alexander Heidi Department of Biological Sciences, Idaho State University, 83204, Pocatello, ID, USA aut Fujimoto Esther Department of Neurobiology and Anatomy, University of Utah, 843123, Salt Lake City, UT, USA aut Sherry Megan Department of Biological Sciences, Idaho State University, 83204, Pocatello, ID, USA aut Petty David Department of Biological Sciences, Idaho State University, 83204, Pocatello, ID, USA aut Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/1(2007-01-01), 87-106 0272-4340 27:1<87 2007 27 10571 https://doi.org/10.1007/s10571-006-9120-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-006-9120-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Groome James Department of Biological Sciences, Idaho State University, 83204, Pocatello, ID, USA aut NATIONALLICENCE 700 1- Alexander Heidi Department of Biological Sciences, Idaho State University, 83204, Pocatello, ID, USA aut NATIONALLICENCE 700 1- Fujimoto Esther Department of Neurobiology and Anatomy, University of Utah, 843123, Salt Lake City, UT, USA aut NATIONALLICENCE 700 1- Sherry Megan Department of Biological Sciences, Idaho State University, 83204, Pocatello, ID, USA aut NATIONALLICENCE 700 1- Petty David Department of Biological Sciences, Idaho State University, 83204, Pocatello, ID, USA aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/1(2007-01-01), 87-106 0272-4340 27:1<87 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer