MODULATION OF A RETINAL CALCIUM CURRENT

描述（改编自申请人摘要）：钙是一种 神经元中的一种重要成分， 从神经递质释放到神经元 死亡因此，细胞质游离钙水平的波动 预计将发挥重要的生理和生化作用。一 可兴奋细胞中钙波动的来源是通过电压- 依赖钙通道。在鲶鱼的视网膜中， 水平细胞含有持续电压激活的钙通道 据推测，它在视网膜病变中具有生理作用， 处理.然而，人们对调控机制知之甚少 以及通过这些通道调节钙。的重要途径 许多神经元调节它们的电压依赖性通道是通过 第二信使系统的作用。因此，这一提议是 旨在确定第二信使系统对钙的作用， 在培养的，分离的鲶鱼水平细胞中的通道活动。的 具体目标是：（1）确定第二信使系统 电压依赖性钙电导调节的基础;（2） 为了描述这些第二信使系统的调节， 鲶鱼的水平细胞，因为它们涉及到电压的调制- 依赖性钙电流;（3）确定 多种第二信使途径在钙调节中的作用 渠道活动。这些具体目标将通过一个 结合全细胞电压钳的多学科方法 记录，单通道切除和细胞上补丁技术 分析和Fura-2成像技术。从这些获得的结果 研究将大大有助于我们理解的作用， 水平细胞和其他神经元中的钙。

DESCRIPTION (Adapted from applicant's abstract): Calcium is an essential component in neurons which is involved in a variety of cellular processes ranging from neurotransmitter release to neuronal death. Therefore, fluctuations in the level of cytoplasmic free calcium are expected to play a major physiological and biochemical role. One source of calcium fluctuation in excitable cells is through voltage- dependent calcium channels. In the catfish retina, second order horizontal cells contain a sustained voltage-activated calcium channel which has been hypothesized to have a physiological role in retinal processing. However, little is known about the mechanisms of regulation and modulation of calcium through these channels. An important way in which many neurons modulate their voltage-dependent channels is through the action of second messenger systems. Therefore, this proposal is designed to determine the role of second messenger systems on calcium channel activity in cultured, isolated catfish horizontal cells. The specific aims are: (1) to identify the second messenger systems underlying the modulation of voltage-dependent calcium conductance; (2) to characterize the regulation of these second messenger systems in catfish horizontal cells as they relate to modulation of the voltage- dependent calcium current; and (3) to determine the interactions between multiple second messenger pathways in their modulating role of calcium channel activity. These specific aims will be carried out using a multidisciplinary approach combining whole-cell voltage clamp recordings, excised and on-cell patch techniques for single channel analysis and fura-2 imaging techniques. Results obtained from these studies will contribute greatly to our understanding of the role of calcium in the horizontal cells as well as other neurons.