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2016 ; 10
(6
): 478-97
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Dynamical characterization of inactivation path in voltage-gated Na(+) ion
channel by non-equilibrium response spectroscopy
#MMPMID27367642
Pal K
; Gangopadhyay G
Channels (Austin)
2016[Nov]; 10
(6
): 478-97
PMID27367642
show ga
Inactivation path of voltage gated sodium channel has been studied here under
various voltage protocols as it is the main governing factor for the periodic
occurrence and shape of the action potential. These voltage protocols actually
serve as non-equilibrium response spectroscopic tools to study the ion channel in
non-equilibrium environment. In contrast to a lot of effort in finding the
crystal structure based molecular mechanism of closed-state(CSI) and open-state
inactivation(OSI); here our approach is to understand the dynamical
characterization of inactivation. The kinetic flux as well as energetic
contribution of the closed and open- state inactivation path is compared here for
voltage protocols, namely constant, pulsed and oscillating. The non-equilibrium
thermodynamic quantities used in response to these voltage protocols serve as
improved characterization tools for theoretical understanding which not only
agrees with the previously known kinetic measurements but also predict the
energetically optimum processes to sustain the auto-regulatory mechanism of
action potential and the consequent inactivation steps needed. The time dependent
voltage pattern governs the population of the conformational states which when
couple with characteristic rate parameters, the CSI and OSI selectivity arise
dynamically to control the inactivation path. Using constant, pulsed and
continuous oscillating voltage protocols we have shown that during depolarization
the OSI path is more favored path of inactivation however, in the hyper-polarized
situation the CSI is favored. It is also shown that the re-factorisation of
inactivated sodium channel to resting state occurs via CSI path. Here we have
shown how the subtle energetic and entropic cost due to the change in the
depolarization magnitude determines the optimum path of inactivation. It is shown
that an efficient CSI and OSI dynamical profile in principle can characterize the
open-state drug blocking phenomena.
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