Weak acid permeability through lipid bilayer membranes. Role of chemical reactions in the unstirred layer

The premeabilities of planar lipid bilayer (egg phosphatidylcholine-decane) membranes to butyric and formic acids were measured by tracer and pH electrode techniques. The purposes of the study were (a) to establish criteria for the applicability of each method and (b) to resolve a discrepancy between previously published permeabilities determined using the different techniques. Tracer fluxes of butyric acid were measured at several concentrations and pH's. Under symmetrical conditions the one-way flux of butyric acid(J) is described by 1/J = 1/Pul ([HA] + [A-]) + 1/Pm([HA]), where Pul and Pm are the unstirred layer and membrane permeability coefficients. Pm determined in this manner is 950 x 10(4) cm s-1. Published values for the butyric acid permeability for egg phosphatidylcholine-decane bilayers are 11.5 x 10(-4) (Wolosin and Ginsburg, 1975) and 640 x 10(-4) cm s-1 (Orbach and Finkelstein, 1980). Wolosin and Ginsburg measured net fluxes from a solution of pH = Pka into an unbuffered solution containing a pH electrode. Orbach and Finkelstein measured tracers fluxes under symmetrical conditions at pH 7.4. We reproduced the results of Wolosin and Ginsburg and showed that their apparently low Pm was caused by unstirred layer effects in their poorly buffered solutions. The permeability to formic acid (pKa = 3.75) measured by both tracer and pH electrode techniques was approximately 10(-2) cm s-1. However, if pm greater than Pul, the pH electrode technique cannot be used for measuring the permeabilities of weak acids with pKa's greater than approximately 4.