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bioRxiv · 10.1101/2023.01.25.525351

Aluminium alters excitability by inhibiting calcium, sodium and potassium currents in bovine chromaffin cells.

Baraibar, A. M.·de Pascual, R.·Jimenez, V.·Hernandez, N.·Aguirregabiria, I. E.·Hernandez-Guijo, J. M.
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Abstract

Aluminium (Al3+) has long been related to neurotoxicity and neurological diseases. This study aims to describe the specific actions of this metal on cellular excitability and neurotransmitter release. Al3+ reduced intracellular calcium concentrations around 25% and decreased catecholamine secretion in a dose-dependent manner, with an IC50 of 89.1 M. Al3+ blocked calcium currents in a time- and concentration-dependent manner with an IC50 of 560 M. This blockade was irreversible, since it did not recover after wash-out. Moreover, Al3+ produced a bigger blockade on N-, P- and Q-type calcium channels subtypes (69.5%) than on L-type channels subtypes (50.5%). Sodium currents were also inhibited by Al3+ in a time- and concentration-dependent manner, 24.3% blockade at the closest concentration to the IC50 (419 M). This inhibition was reversible. Voltage-dependent potassium currents were non-significantly affected by Al3+. Nonetheless, calcium/voltage-dependent potassium currents were inhibited in a concentration-dependent manner, with an IC50 of 447 M. This inhibition was related to the depression of calcium influx through voltage-dependent calcium channels subtypes coupled to BK channels. In summary, the blockade of these ionic conductances altered cellular excitability that reduced the action potentials firing and so, the neurotransmitter release and the synaptic transmission. These findings prove that aluminium has neurotoxic properties because it alters neuronal excitability by inhibiting the sodium currents responsible for the generation and propagation of impulse nerve, the potassium current responsible for the termination of action potentials, and the calcium current responsible for the neurotransmitters release.

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Baraibar, A. M., de Pascual, R., Jimenez, V., Hernandez, N., Aguirregabiria, I. E., Hernandez-Guijo, J. M.. 2023-01-25. Aluminium alters excitability by inhibiting calcium, sodium and potassium currents in bovine chromaffin cells.. https://doi.org/10.1101/2023.01.25.525351

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