Neuroscience Research Centre and Department of Physiology, Medical School, Shahid Beheshti Medical Sciences University, Evin, Tehran, Iran.
Eur J Pharmacol. 2010 Sep 10;642(1-3):56-65. doi: 10.1016/j.ejphar.2010.05.031.
Electrophysiological dysfunction of Purkinje cells causes cerebellar ataxia. Recent studies indicated that 4-aminopyridine (4-AP) can prevent the attacks in patients with episodic ataxia type 2. However, the cellular mechanism(s) by which 4-AP might be beneficial for the improvement of motor function remain unclear. Here, electrophysiological and behavioural consequences of in vivo co-treatment with 4-AP against 3-acetylpyridine (3-AP)-induced ataxia in rats were assessed. Combined treatment with 4-AP partially improved motor behaviour compared to the ataxic rats. Treatment with 3-AP alone induced plastic alterations in the cells' intrinsic properties, so that the latency of the initial neural spike was significantly increased (Pb 0.001); however, both instantaneous firing frequency and amplitude of calcium spikes were significantly (Pb 0.001) suppressed. 3-AP treatment also resulted in significant decrease in the duration of action potential (Pb 0.05) and the amplitude of afterhyperpolarization ((Pb 0.05) as well as post-stimulus hyperpolarization potentials (Pb 0.001). Purkinje cells in rats co-treated with 4-AP, however, fired predominantly in rhythmic bursts. The mean amplitude of Ca2+ spikes was significantly (Pb 0.001) greater compared to ataxic rats, but similar to control value. As evidenced by a significant decrease (Pb 0.001) in the first spike latency, the cells' intrinsic excitability was also increased. In 4-AP co-treated group, the duration of action potential was also significantly lengthened (Pb 0.001) compared to control and 3-AP group. These results suggest that modulation of intrinsic electrical properties and potentiation of Ca2+ channels function caused by in vivo 4-AP treatment is likely to be partly responsible for its neuroprotective action.
浦肯野细胞的电生理功能障碍导致小脑共济失调。最近的研究表明，4-氨基吡啶（4-AP）可预防发作性共济失调 2 型患者的发作。然而，4-AP 改善运动功能的细胞机制尚不清楚。在这里，评估了体内联合应用 4-AP 对大鼠 3-乙酰吡啶（3-AP）诱导的共济失调的电生理和行为后果。与共济失调大鼠相比，联合应用 4-AP 部分改善了运动行为。单独用 3-AP 处理会导致细胞固有特性发生塑性改变，从而使初始神经峰的潜伏期显著增加（Pb 0.001）；然而，钙峰的瞬时放电频率和幅度均显著（Pb 0.001）降低。3-AP 处理还导致动作电位持续时间（Pb 0.05）和超极化后电位（Pb 0.05）幅度显著降低。然而，用 4-AP 联合处理的大鼠浦肯野细胞主要以节律性爆发方式放电。钙峰的平均幅度明显大于共济失调大鼠（Pb 0.001），但与对照值相似。由于第一峰潜伏期显著降低（Pb 0.001），细胞固有兴奋性也增加。在 4-AP 联合处理组中，动作电位的持续时间也显著延长（Pb 0.001），与对照和 3-AP 组相比。这些结果表明，体内 4-AP 处理对固有电生理特性的调节和钙通道功能的增强可能是其神经保护作用的部分原因。
