Ultrasteep voltage dependence in a membrane channel.

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Abstract
A mechanism for regulating voltage-gated channels is presented. The treatment amplifies the effect of the applied membrane potential resulting in a dramatic increase in the channel''s voltage dependence. Addition of a large polyvalent anion to the medium bathing a phospholipid bilayer containng the voltage-dependent channel from the mitochondrial outer membrane, VDAC, induced upto a 12-fold increase in the channel''s voltage sensitivity. The highest polyvalent anion concentration tested resulted in an e-fold conductance change for a 0.36-mV change in membrane potential. On the low end, a concentration of 2 .mu.M resulted in a 50% increase in VDAC voltage dependence. A mechanism based on polyvalent anion accumulation in the access resistance region at the mouth of the pore is consistent with all findings. Perhaps the voltage dependence of voltage-gated channels is amplified in vivo by polyvalent ions. If so, the control of excitable phenomena may be under much finer regulation than that provided by membrane potential alone.

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