title: Kinetic model of Nav1.5 channel provides a subtle insight into slow inactivation associated excitability in cardiac cells.
abstract: Voltage-gated sodium channel Nav1.5 has been linked to the cardiac cell excitability and a variety of arrhythmic syndromes including long QT, Brugada, and conduction abnormalities. Nav1.5 exhibits a slow inactivation, corresponding to a duration-dependent bi-exponential recovery, which is often associated with various arrhythmia syndromes. However, the gating mechanism of Nav1.5 and the physiological role of slow inactivation in cardiac cells remain elusive. Here a 12-state two-step inactivation Markov model was successfully developed to depict the gating kinetics of Nav1.5. This model can simulate the Nav1.5 channel in not only steady state processes, but also various transient processes. Compared with the simpler 8-state model, this 12-state model is well-behaved in simulating and explaining the processes of slow inactivation and slow recovery. This model provides a good framework for further studying the gating mechanism and physiological role of sodium channel in excitable cells.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Jiuping
authors.initials: J
authors.lastname: Ding
mesh_terms: D002460:Cell Line; D004594:Electrophysiology; D006801:Humans; D007700:Kinetics; D008962:Models, Theoretical; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel