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: on e at positive potentials and the other at negative potentials. The ene rgetics of VDAC gating are quite different when measured in the presen ce or absence of an ion gradient. A positive potential on the high-sal t side results in channel closure at lower transmembrane potentials. T he midpoint potential (V-0) shifted from 25 to 5.7 mV, with an activit y gradient for KCl of 0.6 versus 0.06, The opposite occurred for negat ive potentials on the high-salt side (V-0 shifted from -25 to -29 mV), Thus the salt gradient favored closure for one gating process and ope ning for the other. These results could be explained if part of;he ele ctrochemical potential of the gradients present were transferred to th e gating mechanism. If the kinetic energy of the ion flow were coupled to the gating process, the effects of the gradient would depend on th e 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 correl ated 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 direc tion with the voltage gating process in VDAC, which is believed to inv olve the movement of a positively charged portion of the wall of the c hannel out of the membrane.