EFFECT OF DRUGS ON VOLTAGE-DEPENDENT IONIC CONDUCTANCE IN MEMBRANES

该项目的目的是更好地了解药物如何影响 膜中离子电导的机制， 电压依赖性和兴奋性。 最近的重点是 分子氧活性衍生物对龙虾的影响 神经肌肉接头 氧气和这些衍生物 作为多种生理和病理疾病的病原体， 过程，如粒细胞的杀菌作用，衰老， 缺血再灌注损伤 我们发现1微摩尔氢 过氧化物可逆地抑制诱发兴奋性连接电位 （ejp）。 这种作用不作用于谷氨酸突触后受体，因为 当外源性地施用谷氨酸盐时， 应用于制备。 浓度超过0.1毫摩尔 过氧化氢，过氧化物抑制仅部分消除， 谷氨酸的存在。 因此，在高浓度下，突触后 受体受到抑制。 硫脲预处理，一种自由基 清除剂，提供了一些保护，防止过氧化物抑制。 这 有证据表明，至少部分过氧化物抑制作用是 由羟基自由基介导。 部分过氧化物抑制 也可能是由于氢过氧化物的产生和膜脂 过氧化作用 氧分压升高对 鱿鱼巨型突触也在研究中。

The purpose of this project is to better understand how drugs affect the mechanisms of the ionic conductance in membranes which are voltage-dependent and excitable. Emphasis has recently focused on the effect of the reactive derivatives of molecular oxygen on the lobster neuromuscular junction. Oxygen and these derivatives have been implicated as causative agents in a wide number of physiological and pathological processes, such as the bactericidal action of granulocytes, aging, and ischemic reperfusion injury. We have found that 1 micromolar hydrogen peroxide inhibits reversibly the evoked excitatory junction potential (ejp). This effect is not on the glutamate post-synaptic receptor, since this peroxide inhibition is abolished when glutamate is exogeneously applied to the preparation. At concentrations above 0.1 millimolar hydrogen peroxide, the peroxide inhibition is only partially abolished in the presence of glutamate. Thus, at high concentrations, the post-synaptic receptor is inhibited. Pretreatment with thiourea, a free radical scavenger, provides some protection against the peroxide inhibition. This is evidence suggesting that at least part of the peroxide inhibition is mediated by the hydroxyl free radical. Part of the peroxide inhibition might also be due to hydroperoxide production and membrane lipid peroxidation. The effect of elevated partial pressures of oxygen on the squid giant synapse is also being investigated.