Effects Of Flunarizine Hydrochloride On The Persistent Sodium Currents Of Isolated Rat CA1 Hippocampal Pyramidal Neurons Under Ischemia-like Condition In Vitro

Objective: The purpose of the researches is to explore the mechanism of the ischemia-induced neuronal injury and the mechanism of neuroprotective effect of flunarizine hydrochloride by detecting the variation of the persistent sodium current of rat hippocampal CA1 pyramidal neurons under ischemia-like condition and to explore the effect of flunarizine hydrochloride on the variation of the persistent sodium current induced by ischemia.Materials and Methods: The researches included two parts. (1):Whole-cell patch-clamp technique was used to detect the variation of the persistent sodium current in enzymatically isolated rat CA1 hippocampal pyramidal neurons induced by ischemia-like condition. Ischemia-like condition is made by glucose and oxygen deprivation. (2): Flunarizine hydrochloride of different concentrations were applied to rat CA1 hippocampal pyramidal neurons under ischemia-like condition, then using the patch-clamp technique to record the whole-cell persistent sodium current and observe the effect on the variation of the persistent sodium current induced by ischemia.Results: The researches found out (1): Three and five minutes after the ischemia occurred, the amplitude of the persistent sodium currentincreased to 1.59±0.26 times and 2.92 ± 0.46 times respectively. There is a significantly enhancement compared to the current before ischemia occurred (P <0.05). (2): 1.0 mol.L-1, 3.0 mol.L-1 10.0mol.L-1 flunarizine hydrochloride significantly inhibits the increase of the persistent sodium current induced by ischemia (P<0.05). But 0.1 mol.L-1 flunarizine hydrochloride failed to inhibit the current(P>0.05).Conclusions: The increase of the persistent sodium induced by ischemia may play a major role in the ischemia-induced neuronal injury, and flunarizine hydrochloride acts as neuroprotective agent through inhibiting the enhancement of persistent sodium current under ischemia condition.