Membrane surface potential changes may alter drug interactions: an example, acetylcholine and curare

Abstract

Curare is known to be less effective as an acetycholine antagonist when the divalent cation concentration of the extracellular solution is increased. This observation can be accounted for by the negative surface potential on the end plate; an increase in divalent cation concentration decreases the negativity of the surface potential and thereby lowers the concentrations of cations at the membrane-solution interface. The concentration of divalent cations, such as curare, will be reduced more than the concentration of univalent cations, such as acetylcholine. The observations can be accounted for by a surface potential of about -50 millivolts. The same principle can explain the reported actions of divalent cations on the affinity of receptors for acetylcholine. The effects of surface potential on concentrations at active sites may play an important role in drug interactions.