Evidence for titratable gating charges controlling the voltage dependence of the outer mitochondrial membrane channel, VDAC.
A voltage-dependent anion-selective channel, VDAC, is found in outer mitochondrial membranes. VDAC's conductance is known to decrease as the transmembrane voltage is increased in either the positive or negative direction. Charged groups on the channel may be responsible for this voltage dependence by allowing the channel to respond to an applied electric field. If so, then neutralization of these charges would eliminate the voltage dependence. Channels in planar lipid bilayers which behaved normally at pH 6 lost much of their voltage dependence at high pH. Raising the pH reduced the steepness of the voltage dependence and raised the voltage needed to close half the channels. In contrast, the energy difference between the open and closed state in the absence of a field was changed very little by the elevated pH. The groups being titrated had an apparent pK of 10.6. From the pK and chemical modification, lysine epsilon amino groups are the most likely candidates responsible for VDAC's ability to respond to an applied electric field.
K A
KA
Bowen
K
K
Tam
M
M
Colombini
D000818:Animals; D001120:Arginine; D002164:Camphor / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D005026:Ethylene Glycols / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents / Q000494:pharmacology; D007425:Intracellular Membranes / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008051:Lipid Bilayers; D008433:Mathematics; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000502:physiology*; D008930:Mitochondria, Liver / Q000502:physiology*; D008954:Models, Biological; D010636:Phenols; D018272:Porins; D051381:Rats; D050994:Voltage-Dependent Anion Channels
D005026:Ethylene Glycols; D007202:Indicators and Reagents; D007473:Ion Channels; D008051:Lipid Bilayers; D008565:Membrane Proteins; D010636:Phenols; D018272:Porins; D050994:Voltage-Dependent Anion Channels; C034604:4-hydroxyphenethylene glycol; C023633:camphorquinone-10-sulfonic acid; D002164:Camphor; D001120:Arginine