@article{MTMT:3192921,
	title = {Regulation of Na+ channel inactivation by the DIII and DIV voltage-sensing domains.},
	url = {https://m2.mtmt.hu/api/publication/3192921},
	author = {Hsu, EJ and Zhu, W and Schubert, AR and Voelker, T and Varga, Zoltán and Silva, JR},
	doi = {10.1085/jgp.201611678},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {149},
	unique-id = {3192921},
	issn = {0022-1295},
	abstract = {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.},
	year = {2017},
	eissn = {1540-7748},
	pages = {389-403}
}