The mitochondrial outer membrane channel, VDAC, is regulated by a synthetic polyanion

A synthetic polyanion has been found to modulate the properties of the mitochondrial outer membrane channel, VDAC. This 10 kDa polyanion, first synthesized and described by Konig and co-workers, is a 1:2:3 copolymer of methacrylate, maleate, and styrene. It had been shown to interfere with the access of metabolites to the mitochondrial inner spaces. Here we show that, at nanomolar levels, the polyanion increases the voltage dependence of VDAC channels over 5-fold. Some channels seem to be totally blocked while others display the higher voltage dependence and are able to close at very low membrane potentials (5 mV). At 27 micrograms/ml polyanion, VDAC channels are closed while inserted into liposomes in the absence of any applied potential. The closed state of VDAC induced by the polyanion has similar properties to the closed state induced by elevated membrane potentials. The physical size of the polyanion-induced closed state (in VDAC-containing liposomes) is about 0.9 nm in radius. How this estimate fits with estimates of the channel's open state and estimated volume changes between the open and closed states, is discussed.