MODULATION OF A RETINAL CALCIUM CURRENT

说明(摘自申请者的摘要)：钙是一种 神经元中的基本成分，参与多种 从神经递质释放到神经元的细胞过程 死亡。因此，胞浆游离钙水平的波动 有望发挥重要的生理生化作用。一 可兴奋细胞中钙波动的来源是通过电压- 依赖性钙通道。在鲶鱼的视网膜中，二级 水平细胞含有持续电压激活的钙通道 它被认为在视网膜中起着生理作用 正在处理。然而，人们对监管机制知之甚少。 并通过这些通道调节钙离子。一条重要的途径 许多神经元调节其电压依赖的通道是通过 第二信使系统的动作。因此，这项建议是 旨在确定第二信使系统在钙离子上的作用 培养的、分离的叉尾鱼水平细胞中的通道活动。这个 具体目标是：(1)识别第二信使系统 电压依赖性钙电导调制的基础；(2) 为了表征这些第二信使系统的调节 当它们与电压的调制有关时，鲶鱼水平细胞- 依赖钙电流；以及(3)确定相互作用 多条第二信使通路在钙离子调节中的作用 通道活动。这些具体目标将通过一个 结合全电池电压钳位的多学科方法 用于单通道的记录、切除和在单元贴片技术 分析和Fura-2成像技术。从这些数据中获得的结果 研究将极大地有助于我们理解 水平细胞和其他神经元中的钙离子。

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.