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.

Time-dependent actions of aluminates on membrane and action potentials of snail neurons.

Aluminum (Al) is one of the elements, which is frequently subjected to experiments, however, the neurological observations with it are rather conflicting. The cause of this controversiality is not known but relates to some human disorders such as Alzheimer's disease and others as well. We studied the time-dependent actions of AlCl3 base solutions on resting membrane potential (Em), input resistance (Rin) and spike shape in giant neurons of the snail Helix pomatia L. at pH 7.7 and room temperature (22-24 degrees C) by use of intracellular technique. We reported significant differences in the effectiveness of the various Al solutions depending on the time of storage before use in the experiments (0, 2 and 6 days at room temperature). Freshly prepared and applied Al solutions caused a significant and dose-dependent depolarization with a concomitant decrease of Rin and the amplitude of the action potentials, but the 6 days solutions induced a hyperpolarization. Ouabain (0.1 mM) antagonized the hyperpolarization. The pH (7.1 or 7.7) and the time of the storage in combination also modified the direct membrane effects. Our experiments show that Al can induce differential membrane effects depending on the presence of various aluminum compounds. Namely, the predominate aluminum-monomer at pH 7.7 the Al(OH)4- might cause depolarization but the polynuclear aluminum complexes after polymerization of the monomers could hyperpolarize the neuronal membrane. We suppose, that the time-dependent equilibrium of various aluminum complexes plays a role in generating controversies in this field and emphasize again the importance of standardization of the experimental protocol.

Aluminum enhances the voltage activated sodium currents in the neurons of the pond snail Lymnaea stagnalis L.

1. The effects of aluminum on voltage activated sodium currents (VASCs) were investigated by using the conventional two-electrode voltage clamp technique in Lymnaea stagnalis L. neurons. The peak amplitude, kinetics, and voltage-dependence of activation and inactivation of the sodium currents were studied in the presence of 5-500 microM AlCl3, at pH = 7.7. 2. There was a significant concentration-dependent increase in the peak amplitude of sodium currents after Al treatment, ED50 = 67 microM. The threshold concentration of the enhancement was 50 microM. The maximal peak increase of 143% was caused by a 500 microM aluminum. The action of aluminum on VASCs developed slowly, and it is not recovered by washing within 20 min. 3. There was little alteration of the voltage-dependence of the current. It was not a significant effect on the activation- and inactivation time constants of INa, but the steady-state inactivation curve shifted to negative direction on the voltage axis in the presence of Al. 4. The leak currents were not influenced by aluminum up to the highest concentration applied.

Comparative electrophysiological aspects of aluminum actions on central neurons and neuronal synapses of invertebrate and vertebrate animals.

Aluminum compounds (Al) increased the membrane potential (Em) and decreased the input resistance (Rin) of identified snail neurons. The neuronal excitability increased after Al withdrawal in the washing period. Cumulative Al applications caused dose-dependent modulation of Em and Rin in most of the studied neurons. Two phase actions were recorded on stimulus evoked excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) at pH 6.5-6.9. The Al induced facilitation followed by attenuation were statistically significant, time- and dose-dependent events. They could be recorded at each Em. Low affinity and slow binding kinetics could characterize the Al actions on the neurons. Al showed pH- dependent suppression of EPSPs or EPSCs in some neurons. Our findings are partially comparable with Al induced electrophysiological and pharmacological modifications reported on vertebrate neurons.