CHLORIDE REGULATION OF PHOTORECEPTOR NEUROTRANSMISSION

光感受器神经传递的氯化物调节

• 批准号: 2711106
• 负责人: WALLACE B THORESON
• 金额: $ 9.86万
• 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/2711106
• 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，以控制此时的递质释放 视觉中关键的第一个突触。光感受器的调节 氯化物的神经传递会在许多方面影响视力。为 例如，在持续照明期间氯水平的变化可能 在接受后适应中发挥作用；氯离子通量在 锥体感受野周围的光照可以调节 周围对抗的强度；和活动依赖的变化 氯化物应该改变光反应的开启和关闭之间的平衡 (这可能是视网膜神经节的敏感性增强的原因) 细胞对缺血的影响)。为了评估氯离子调节的可能功能， 理解负责的机制(S)是至关重要的 光感受器递质释放的抑制作用 细胞外氯化物的减少。 除了抑制水平和双极的光诱发电流 细胞，减少氯化物抑制二氢吡啶敏感的钙 光感受器的电流。二氢吡啶对该电流的抑制作用 拮抗剂减少二级视网膜神经元的光反应。 因此，我们假设，光诱发的抑制 视网膜二级神经元中的电流可能会因 还原诱导的光感受器钙电流的抑制 在氯化物中。这项提议的两个主要目的是检验这一点 进一步的假设，并分析机制(S)，氯可能通过 影响钙通道功能。全电池和单通道贴片 将使用钳位记录来研究氯离子敏感性 光感受器钙电流，以及由光和 大脑皮层水平和双极细胞的自发量子释放 两栖动物的视网膜。这些实验应该会让我们了解 氯离子调节的光感受器机制和 为未来研究这一可能的功能提供了良好的基础 新确定的监管机制。