TY - JOUR AU - Hsu, EJ AU - Zhu, W AU - Schubert, AR AU - Voelker, T AU - Varga, Zoltán AU - Silva, JR TI - Regulation of Na+ channel inactivation by the DIII and DIV voltage-sensing domains. JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 149 PY - 2017 IS - 3 SP - 389 EP - 403 PG - 13 SN - 0022-1295 DO - 10.1085/jgp.201611678 UR - https://m2.mtmt.hu/api/publication/3192921 ID - 3192921 N1 - Megjegyzés-27145423 Megjegyzés-27133549 OA gold AB - Functional eukaryotic voltage-gated Na+ (NaV) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical NaV channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair NaV channel inactivation. These locations include the DIII-DIV linker, the DIII S4-S5 linker, and the DIV S4-S5 linker. Our results show that, within the 10-ms timeframe of fast inactivation, the DIV-VSD is the primary regulator of inactivation. However, after longer 100-ms pulses, the DIII-DIV linker slows DIII-VSD deactivation, and the rate of DIII deactivation correlates strongly with the rate of recovery from inactivation. Our results imply that, over the course of an action potential, DIV-VSDs regulate the onset of fast inactivation while DIII-VSDs determine its recovery. LA - English DB - MTMT ER - TY - JOUR AU - Lukács, Péter AU - Gawali, Vaibhavkumar S AU - Cervenka, Rene AU - Ke, Song AU - Koenig, Xaver AU - Rubi, Lena AU - Zarrabi, Touran AU - Hilber, Karlheinz AU - Stary-Weinzinger, Anna AU - Todt, Hannes TI - Exploring the structure of the voltage-gated Na+ channel by an engineered drug access pathway to the receptor site for local anesthetics JF - JOURNAL OF BIOLOGICAL CHEMISTRY J2 - J BIOL CHEM VL - 289 PY - 2014 IS - 31 SP - 21770 EP - 21781 PG - 12 SN - 0021-9258 DO - 10.1074/jbc.M113.541763 UR - https://m2.mtmt.hu/api/publication/3070626 ID - 3070626 LA - English DB - MTMT ER - TY - JOUR AU - Zarrabi, Touran AU - Cervenka, Rene AU - Sandtner, Walter AU - Lukács, Péter AU - Koenig, Xaver AU - Hilber, Karlheinz AU - Mille, Markus AU - Lipkind, Gregory M AU - Fozzard, Harry A AU - Todt, Hannes TI - A molecular switch between the outer and the inner vestibules of the voltage-gated Na+ channel JF - JOURNAL OF BIOLOGICAL CHEMISTRY J2 - J BIOL CHEM VL - 285 PY - 2010 IS - 50 SP - 39458 EP - 39470 PG - 13 SN - 0021-9258 DO - 10.1074/jbc.M110.132886 UR - https://m2.mtmt.hu/api/publication/3070588 ID - 3070588 LA - English DB - MTMT ER -