EFFECT OF DRUGS ON VOLTAGE-DEPENDENT IONIC CONDUCTANCE IN MEMBRANES

药物对膜中电压依赖性离子电导的影响

• 批准号: 4696831
• 负责人: D L GILBERT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696831
• 关键词: action potentials; axon; biophysics; chemical structure function; drug metabolism; drug screening /evaluation; free radicals; hydrogen peroxide; hydroxyl group; ion transport; mathematical model; membrane permeability; membrane potentials; neural conduction; neuromuscular junction; neuropharmacologic agent; neuropharmacology; respiratory oxygen; saltwater environment; synapses; yohimbine

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.

这个项目的目的是为了更好地了解药物是如何影响 膜中离子电导的机理是 电压依赖且可兴奋的。最近重点放在了 分子氧的活性衍生物对龙虾的影响 神经肌肉接头。氧气和这些衍生品有牵连 作为病原体在许多生理和病理上 过程，如粒细胞的杀菌作用，老化，以及 缺血再灌注损伤。我们发现1微摩尔氢 过氧化可逆地抑制诱发的兴奋性连接电位 (Ejp)。这种影响对谷氨酸突触后受体没有影响，因为 当谷氨酸被外源抑制时，这种过氧化抑制作用被取消。 应用于制剂。浓度高于0.1毫摩尔 过氧化氢，过氧化氢的抑制作用仅部分消除。 谷氨酸的存在。因此，在高浓度时，突触后 受体被抑制。用自由基硫脲进行预处理 清除剂，提供一些保护，防止过氧化氢的抑制。这 是否有证据表明，过氧化氢抑制的至少一部分是 由羟基自由基介导。过氧化氢抑制的一部分 也可能是由于过氧化氢的产生和膜脂的作用 过氧化。氧分压升高对血液流变学的影响 乌贼巨型突触也在接受调查。