Lyotropic anions. Na channel gating and Ca electrode response.

Abstract

The effects of external anions on gating of Na channels of frog skeletal muscle were studied under voltage clamp. Anions reversibly shift the voltage dependence of peak sodium permeability and of steady state sodium inactivation towards more negative potentials in the sequence: methanesulfonate .ltoreq. Cl- .ltoreq. acetate < Br- .ltoreq. NO3- .ltoreq. SO42- < benzenesulfonate < SCN- < ClO4-; approximately the lyotropic sequence. Voltage shifts are graded with mole fraction in mixtures and are roughly additive to Ca shifts. The peak PNa is not greatly affected. Except for SO42-, these anions did not change the Ca2+ activity of the solutions as measured with the dye murexide. Shifts of gating can be explained as the electrostatic effect of anion adsorption to the Na channel or to nearby lipid. Such adsorption is expected to follow the lyotropic series. Anions also interfere significantly with the response of a Ca-sensitive membrane electrode following the same sequence of effectiveness as the shifts of gating. The lyotropic anions decrease the Ca2+ sensitivity and cause anomalously negative responses of the Ca electrode because these anions are somewhat permeant in the hydrophobic detector membrane.