Proton conductance through phospholipid bilayers: water wires or weak acids?

The proton/hydroxide (H+/OH-) permeability of phospholipid bilayer membranes at neutral pH is at least five orders of magnitude higher than the alkali or halide ion permeability, but the mechanism(s) of H+/OH- transport are unknown. This review describes the characteristics of H+/OH- permeability and conductance through several types of planar phospholipid bilayer membranes. At pH 7, the H+/OH- conductances (GH/OH) range from 2-6 nS cm-2, corresponding to net H+/OH- permeabilities of (0.4-1.7) X 10(-5) cm sec-1. Inhibitors of GH/OH include serum albumin, phloretin, glycerol, and low pH. Enhancers of GH/OH include chlorodecane, fatty acids, gramicidin, and voltages greater than 80 mV. Water permeability and GH/OH are not correlated. The characteristics of GH/OH in fatty acid (weak acid) containing membranes are qualitatively similar to the controls in at least eight different respects. The characteristics of GH/OH in gramicidin (water wire) containing membranes are qualitatively different from the controls in at least four different respects. Thus, the simplest explanation for the data is that GH/OH in unmodified bilayers is due primarily to weakly acidic contaminants which act as proton carriers at physiological pH. However, at low pH or in the presence of inhibitors, a residual GH/OH remains which may be due to water wires, "hydrated defects," or other mechanisms.