ACETYLCHOLINE MODULATION OF ION CHANNELS AND FIRING PATTERNS

乙酰胆碱通过M受体调节 改变多种钠、钙、钾对神经元兴奋性的影响 频道。这种兴奋性的调节在 胆碱能调节觉醒、认知和记忆。的目标是 这项拟议的研究是为了了解毒碱在行动中的变化。 潜在的形成和激发模式方面的调制 特殊的离子通道。膜片钳技术将被用来研究 交感神经内钠、钾、钙通道的控制， 大鼠海马区和多巴胺能神经元通过毒鼠宁刺激。初级阶段 实验准备将是急性分离的神经元，这使得 具有足够速度的电压钳位，以表征调制 动作电位期间流过的大而快的电流。这将延长 以前的工作是使用脑片，其中只有相对较小和缓慢的 电流可以在电压钳下进行研究。我们将直接审查 首次记录动作时动作电位过程中的电流 潜在的波形，在同一细胞中，使用这些波形作为 电压钳位实验中的指令电压。通过使用药理学 分离单个电流沙子的工具执行电流钳位 在乙酰胆碱存在的情况下进行电压钳实验，它应该 可以确定特定通道的调制作用 对兴奋性总体变化有贡献的类型。毒鼠强 离子通道和神经元兴奋性的控制是 大脑的正常运作，有证据表明大脑的 大脑老化。海马神经元M胆碱能调制的变化可能 集中参与阿尔茨海默氏症的症状，而且更好 对相关通道的了解可能会导致新的治疗方法 干预，例如通过使用离子通道阻滞剂来模拟效果 乙酰胆碱。

Acetylcholine acting through muscarinic receptors modulates the excitability of neurons by altering various sodium, calcium, and potassium channels. This modulation of excitability plays a central role in cholinergic regulation of wakefulness, cognition, and memory. The goal of the proposed research is to understand muscarinic changes in action potential formation and firing patterns in terms of modulation of particular ion channels. Patch clamp techniques will be used to study the control of sodium, potassium, calcium channels in sympathetic, hippocampal, and dopamine neurons by muscarinic stimulation. The primary experimental preparation will be acutely isolated neurons, which allow voltage-clamp with sufficient speed to characterize modulation of the large, rapid currents flowing during action potentials. This will extend previous work using brain slices, in which only relatively small and slow currents could be studied under voltage-clamp. We will directly examine currents flowing during action potentials by first recording action potential wave-forms and, in the same cell, using those wave forms as command voltages in voltage clamp experiments. By using pharmacological tools to separate individual current sand performing both current-clamp and voltage-clamp experiments in the presence of acetylcholine, it should be possible to determine the role of modulation of particular channel types in contribution to overall changes in excitability. Muscarinic control of ion channels and neuronal excitability is a basic process for the normal operation of the brain, and evidence suggests changes in the aging brain. Changes in muscarinic modulation of hippocampal neurons may be centrally involved in the symptoms of Alzheimer's disease, and better understanding of the channels involved may lead to novel therapeutic interventions, for example by using ion channel blockers to mimic effects of acetylcholine.