A new model of weak acid permeation through membranes revisited: does Overton still rule?

According to a recent publication by Thomae, A. V., H. Wunderli-Allenspach, and S. D. Krämer (2005. Biophys. J. 89:1802-1811), membrane bilayers are well-permeable to the charged species of aromatic carboxylic acids. At physiological pH, the anions were claimed to be the major diffusing species. In contrast, calculation of the Born energy barrier predicts a 10(5)-fold higher permeability for the uncharged (protonated) form. To test the new model, we now have measured both the current carried by the salicylate anion through solvent-free planar membranes and the amount of protons transported by the neutral species. The corresponding membrane permeabilities of the charged and protonated forms were 4 x 10(-7) cm/s and 1.2 cm/s. These data are in perfect agreement with literature data gathered in the last three decades (compare, e.g., Gutknecht, J., and D. C. Tosteson. 1973. Science. 182:1258-1261). They indicate that the report by Thomae at al. represents an experimental artifact. The well-documented role of neutral species in the permeation process of weak acids and bases across artificial and natural membranes is not in question. Overton still rules.