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- W2464795752 abstract "The assumption of a gated pore in a voltage-sensitive ion channel (VSIC) [Hille, Ion Channels of Excitable Membranes, 2001] treats the channel's nanoworld as the macroworld with shrunken dimensions. It suggests deterministically voltage-dependent opening and closing of ion channels, contrary to the observed stochastic single-channel currents. Another anomaly is neglect of the mutual electrostatic repulsions between the positively charged arg and lys residues in the S4 segments, on grounds of a supposed neutralization by the fewer negatively charged residues in neighboring segments and/or an assumed transmembrane water column [Bezanilla 2008 Neuron 60:456-468; Börjesson, Elinder 2008 Cell Biochem Biophys 52:149-174]. An interdisciplinary model of the way membrane depolarization activates ion channels considers ferroelectric properties [Liu et al. 2012 Phys Rev Lett 108:078103] of resting VSICs [Leuchtag, Voltage-Sensitive Ion Channels, 2008]. In ferroelectric liquid crystals (FLCs) containing branched-chain amino acid (BCAA) (ile, leu, val) sidechains, the dielectric permittivity ε in the ferroelectric phase reaches values over 3000 [Yoshino et al. 1986 Japan J App Phys 25:L416-L418]. Assuming the VSIC with its ubiquitous BCAAs to be a FLC implies that a threshold depolarization changes the channel's phase from ferroelectric to nonpolar, sharply reducing its mean ε. This greatly increases the repulsive Coulomb forces within the S4s, expanding their α-helical pitch, consistent with observed outward S4 movements [Posson, Selvin 2008 Neuron 59:98-109]. The present model postulates that S4 expansion drives an allosteric conformational transition that allows permeant ions to hop along the widened pore domain and percolate [Zallen, The Physics of Amorphous Solids 1983] across the membrane. Observed effects of BCAA replacement with unbranched residues in sodium channels confirm model predictions [Helluin et al. 2001 IEEE Trans Diel Elect Insul 8:637-643; Bendahhou et al. 2007 Biochim Biophys Acta 1768:1440-1447]." @default.
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- W2464795752 date "2016-02-01" @default.
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- W2464795752 title "Variable Electrostatic Repulsion Model of Ion-Channel Activation Vs. Gated Pore with “Neutralized” S4 segments" @default.
- W2464795752 doi "https://doi.org/10.1016/j.bpj.2015.11.1503" @default.
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