pH-dependent actions of aluminum on voltage-activated sodium currents in snail neurons

The pH-dependent actions of aluminum(III) hydroxides (Al(III))on the voltage-activated sodium currents (VASCs) in the giant neurons of the pond snail Lymnaea stagnalis L. were studied by means of a conventional two-electrode voltage-clamp technique. The final concentration of Al(III) was 5-500 microM at pH 7.7, 6.9 or 6.0. A significant and concentration-dependent increase in the peak amplitude of the VASCs was recorded over the entire voltage range at pH 7.7 (EC50 = 100.7 +/- 33.7 microM, n = 9), without alteration of the gating properties. A concentration-dependent decrease in the peak amplitude (IC50 = 175.9 +/- 73.6 microM, n = 6) and concomitant increases in the time constants of activation and inactivation of the VASCs were recorded in slightly acidic media (pH 6.0), whereas there were no changes in the investigated parameters at pH 6.9. A significant increase in the V1/2 of the half-maximal current of the steady-state inactivation resulted on Al(III) application at pH 7.7, but not at pH 6.9 or 6.0. These results suggest that Al(III) can differentially up- and down-modulate the sodium current and related physiological functions to extents dependent on the pH-determined speciation of the Al(III) hydroxides present.