title: Conductance hysteresis in the voltage-dependent anion channel.
abstract: Hysteresis in the conductance of voltage-sensitive ion channels is observed when the transmembrane voltage is periodically varied with time. Although this phenomenon has been used in studies of gating of the voltage-dependent anion channel, VDAC, from the outer mitochondrial membrane for nearly four decades, full hysteresis curves have never been reported, because the focus was solely on the channel opening branches of the hysteresis loops. We studied the hysteretic response of a multichannel VDAC system to a triangular voltage ramp the frequency of which was varied over three orders of magnitude, from 0.5 mHz to 0.2 Hz. We found that in this wide frequency range the area encircled by the hysteresis curves changes by less than a factor of three, suggesting broad distribution of the characteristic times and strongly non-equilibrium behavior. At the same time, quasi-equilibrium two-state behavior is observed for hysteresis branches corresponding to VDAC opening. This enables calculation of the usual equilibrium gating parameters, gating charge and voltage of equipartitioning, which were found to be almost insensitive to the ramp frequency. To rationalize this peculiarity, we hypothesize that during voltage-induced closure and opening the system explores different regions of the complex free energy landscape, and, in the opening branch, follows quasi-equilibrium paths.
authors.affiliation: Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Shay M
authors.initials: SM
authors.lastname: Rappaport
authors.affiliation: Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Oscar
authors.initials: O
authors.lastname: Teijido
authors.affiliation: Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.|Center for Neutron Research, NIST, Gaithersburg, MD 20899.
authors.forename: David P
authors.initials: DP
authors.lastname: Hoogerheide
authors.affiliation: Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Rostovtseva
authors.affiliation: Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.|Mathematical and Statistical Computing Laboratory, Division for Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Berezhkovskii
authors.affiliation: Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Bezrukov
mesh_terms: D015640:Ion Channel Gating; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008564:Membrane Potentials; D050994:Voltage-Dependent Anion Channels / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D050994:Voltage-Dependent Anion Channels