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  -