Conductance Hysteresis in the Voltage-Dependent Anion Channel
Shay M. Rappaport, Oscar Teijido, David Hoogerheide, Tatiana K. Rostovtseva, Alexander M. Berezhkovskii, Sergey M. Bezrukov
In contrast to the voltage gating of ion-selective channels of electrophysiology, the mechanisms of voltage sensitivity of ¿large¿ beta-barrel channels remain obscure, even at the conceptual level. Here we study hysteresis in the conductance response of voltage-dependent anion channels from the outer mitochondrial membrane reconstituted into planar lipid bilayers to low-frequency triangular voltage ramps. We find that within the nearly three orders of magnitude range of the ramp frequencies explored in this study, from 0.5 to 200 mHz, the area of the hysteresis loop does not change by more than threefold, suggesting the existence of a broad distribution of time scales characterizing the process. Application of step-wise voltages of -50 mV promotes relatively slow channel closure; however, upon return to zero voltage the channels quickly return to their open states. As a consequence, for the decreasing (in absolute value) voltages of the ramp that correspond to the channel opening, the relaxation is fast enough to ensure an equilibrium-like behavior within the whole studied range of the ramp frequency. For this reason the system response to the decreasing in amplitude voltages allows for a simple description of the gating in terms of the usual characteristic parameters such as the effective gating charge and voltage of half-effect. Such a description is a fingerprint of the two-state dynamics that underlies the gating. At the same time, specially designed relaxation experiments clearly demonstrate that the gating cannot be described by a two-state Markov model with however complex voltage dependencies of the rate constants. One of the possible explanations for this peculiarity is that the channel explores different regions of the multidimensional free energy landscape when closing and opening during descending and ascending phases of the voltage ramp, respectively.
, Teijido, O.
, Hoogerheide, D.
, Rostovtseva, T.
, Berezhkovskii, A.
and Bezrukov, S.
Conductance Hysteresis in the Voltage-Dependent Anion Channel, European Biophysics Journal, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=917808
(Accessed February 20, 2024)