The voltage-gating process of the voltage-dependent anion channel is sensitive to ion flow

The voltage-dependent anion channel (VDAC) is a voltage-gated channel from the mitochondrial outer membrane. It has two gating processes: one at positive potentials and the other at negative potentials. The energetics of VDAC gating are quite different when measured in the presence or absence of an ion gradient. A positive potential on the high-salt side results in channel closure at lower transmembrane potentials. The midpoint potential (V0) shifted from 25 to 5.7 mV, with an activity gradient for KCl of 0.6 versus 0.06. The opposite occurred for negative potentials on the high-salt side (V0 shifted from -25 to -29 mV). Thus the salt gradient favored closure for one gating process and opening for the other. These results could be explained if part of the electrochemical potential of the gradients present were transferred to the gating mechanism. If the kinetic energy of the ion flow were coupled to the gating process, the effects of the gradient would depend on the mass and velocities of these ions. This was tested by using a series of different salts (KCl, NaCl, LiCl, KBr, K acetate, Na butyrate, and RbBr) under an identical activity gradient. The kinetic energy correlated very well with the measured shifts in free energy of the channel gating. This was true for both polarities. Thus the gating of VDAC is influenced by ion flow. These results are consistent in sign and direction with the voltage gating process in VDAC, which is believed to involve the movement of a positively charged portion of the wall of the channel out of the membrane.