CHLORIDE REGULATION OF PHOTORECEPTOR NEUROTRANSMISSION

光感受器神经传递的氯化物调节

• 批准号: 2888443
• 负责人: WALLACE B THORESON
• 金额: $ 10.15万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2888443
• 关键词: G protein; Urodela; calcium channel; chlorine; cone cell; electrophysiology; horizontal cell; light adaptations; neural transmission; retina; retinal bipolar neuron; second messengers; visual photoreceptor; voltage /patch clamp

Small reductions in extracellular chloride suppress light-evoked currents in second-order retinal neurons. Thus, physiological regulation of chloride in and around photoreceptors may act in concert with photoreceptor membrane voltage to control transmitter release at this critical first synapse in vision. Regulation of photoreceptor neurotransmission by chloride could affect vision in many ways. For example, changes in chloride levels during sustained illumination might play a role in post-receptoral adaption; chloride fluxes during illumination of the cone receptive field surround could adjust the strength of surround antagonism; and activity-dependent changes in chloride should alter the balance between ON and OFF light responses (which could account for the enhanced sensitivity of ON retinal ganglion cells to ischemia). To assess possible functions of chloride regulation, it is essential to understand the mechanism(s) responsible for the suppression of transmitter release from photoreceptors induced by reductions in extracellular chloride. Besides suppressing light-evoked currents in horizontal and bipolar cells, reducing chloride suppresses the dihydropyridine-sensitive calcium current in photoreceptors. Suppression of this current by dihydropyridine antagonists reduces light responses in second-order retinal neurons. Therefore, it is hypothesized that the suppression of light-evoked currents in second order retinal neurons may arise as a consequence of the suppression of photoreceptor calcium currents induced by reductions in chloride. The two major aims of this proposal are to test this hypothesis further and to analyze the mechanism(s) by which chloride may influence calcium channel function. Whole cell and single channel patch clamp recordings will be used to study the chloride sensitivity of photoreceptor calcium currents, as well as currents evoked by light and spontaneous quantal release in horizontal and bipolar cells of the amphibian retina. These experiments should provide an understanding of the photoreceptor mechanisms responsible for chloride regulation and provide a sound basis for future studies into possible functions of this newly identified regulatory mechanism.

细胞外氯离子的少量减少抑制光诱发电流 在二级视网膜神经元中。因此，生理调节 光感受器内和周围的氯化物可能与 光感受器膜电压，以控制在此传递释放 视觉中至关重要的第一个突触光感受器的调节 氯化物的神经传递可以在许多方面影响视力。为 例如，持续光照期间氯化物水平的变化可能 在感受器后适应中发挥作用; 视锥感受野周围的照明可以调节 周围拮抗作用的强度;以及 氯化物会改变开和关光反应之间的平衡 （这可能是ON视网膜神经节敏感性增强的原因 细胞缺血）。为了评估氯化物调节的可能功能， 必须了解负责 光感受器释放递质的抑制 细胞外氯化物的减少。 除了抑制水平和双极的光诱发电流外 细胞，减少氯抑制二氢吡啶敏感的钙 光感受器中的电流二氢吡啶抑制该电流 拮抗剂降低二级视网膜神经元中的光反应。 因此，假设光诱发的抑制 第二级视网膜神经元中的电流可能是 还原诱导的光感受器钙电流的抑制 在氯化物中。本提案的两个主要目的是检验这一点 进一步假设，并分析氯化物可能 影响钙通道功能。全细胞和单通道贴片 钳夹记录将用于研究 光感受器钙电流，以及由光诱发的电流， 水平和双极细胞的自发量子释放 两栖动物的视网膜这些实验应该提供一个理解， 负责氯调节的感光机制， 为今后研究这一系统的可能功能提供良好的基础。 新的监管机制。