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