The Role Of ¦Ä-aminolevulinic Acid (ala) On Rat Hippocampal Ca1 Pyramidal Neuron Excitability And Synaptic Plasticity

In this paper, using the electriphysiological techniques of single cell and brain slices, we studied the effects of ALA on voltage-gated sodium channels in acutely dissociated rat hippocampal CA1 neurons, and the changes of synaptic plasticity and synaptic transmission induced by ALA. Moreover, we investigated the possible mechanisms.Techniques: slice and cell patch-clamp, fEPSPs recording Results:1) Effects of ALA on voltage-gated sodium channels in rat hippocampal CA1 neuronsWhen the voltage-gated potassium channels and calcium channels were blocked, we could record a TTX-sensitive voltage-gated sodium channels currents in acutely dissociated rat hippocampal CA1 neurons. It was found that, low concentrations of ALA increased in the amplitude of sodium currents, whereas high concentrations of ALA decreased the amplitude of sodium currents, which were both unreversible. The increase induced by low concentrations of ALA could be prevented completely by anti-oxidant, while the decrease induced by high concentrations of ALA could be reversed partly by anti-oxidant. Different concentrations of ALA all significantly delayed the recovery time of sodium channels, which also could be reversed partly by anti-oxidant. These results proved the involvement of pro-oxidative effect of ALA. All concentrations of ALA shifted the steady-state activation and inactivation curves towards hyperpolarization, decreased the threshold of channel openning and enhanced the excitability of neurons, moreover, this effect could not be blocked by anti-oxidant, suggesting that ALA might modulate sodium channels by other pathways. Considering the structure similarity between ALA and GABA, blocking GABAa receptors did not change the effects of ALA on sodium channels, while activating GABAb receptors mimicked the effects of ALA on sodium channels, indicating the possible involvement of GABAb receptors in the other cellular actions of ALA. Additionally, the modulation of ALA on sodium channels was not state-dependent.2) Effects of ALA on synaptic plasticity and spontaneous post-synaptic currents in rat hippocampal CA1 neuronsDue to the important roles that the excitability of neurons and post-synaptic action potential firing play in the modulation of synaptic plasticity, we studied the effects of ALA at the synaptic level as well as the possible mechanisms. It was found, at the pre-synaptic, ALA enhanced paired-pulse facilitation, which showed ALA increased the release of pre-synaptic neurotransmitters; at the post-synaptic, ALA...