ION CHANNELS IN THE NERVOUS SYSTEM

描述：神经系统中几乎所有的离子通道都是 多基因家族的成员。 这种丰富的基因导致了 电压门控和配体门控的显著分子多样性 离子通道 我们正在使用多学科方法研究钠 在神经系统中作为电信号基础的钠通道（NaChs） 系统 本研究有两个目的：（1）继续 鉴定和表征新的NaCh基因和（2）稍后测试 可能的生理作用subserved这些氯化钠亚型。 我们估计老鼠（和人类一样）至少有10个NaCh基因。 我们 已经分离并鉴定了一个全长cDNA和一个 新型NaChs的部分cDNA。 一个cDNA是在大肠杆菌中最丰富的NaCh。 在脑中表达，并且在神经元和神经胶质中表达。 第二个NaCh是 可能只在周围神经系统中表达。 我们正在使用 各种分子、细胞和生物物理技术来研究 它们的分布、丰度和电生理特性 NaChs第二个目标围绕着一个问题， 回答任何离子通道：为什么有这么多的基因？ 一个简单 答案是，所有子类型都具有类似的通道属性， 专业角色。 上述研究为检验提供了依据 这些NaCh亚型的假设角色。 两个功能将是 测试：优先靶向不同的细胞结构域， 第二信使系统的差异调节。 这些研究将有助于我们了解分子 钠电流的成分和细胞调节。 他们还将 为理解人类神经和 肌肉疾病。 成人骨骼肌中的已知突变 NaCh基因可引起过度兴奋，有时会出现暂时性麻痹。 预期突变也发生在其他NaCh基因中，大多数 在神经系统中表达。

DESCRIPTION: Virtually all ion channels in the nervous system are members of multigene families. This abundance of genes results in a remarkable molecular diversity of both voltage-gated and ligand-gated ion channels. We are using a multidisciplinary approach to study sodium channels (NaChs) which underlie electrical signaling in the nervous system. The proposed research has two goals: (1) to continue identifying and characterizing novel NaCh genes and (2) later to test possible physiological roles subserved by these NaCh subtypes. We estimate that rats (like humans) have at least ten NaCh genes. We have isolated and are characterizing one full-length cDNA and one partial cDNA for novel NaChs. One cDNA is the most abundant NaCh in brain and is expressed in both neurons and glia. The second NaCh is probably expressed only in the peripheral nervous system. We are using a variety of molecular, cellular, and biophysical techniques to study the distribution, abundance, and electrophysiological properties of these NaChs. The second goal centers around a question which has not been answered for any ion channel: why are there so many genes? A simple answer is that all subtypes have similar channel properties but specialized roles. The above studies provide a basis for testing hypothetical roles for these NaCh subtypes. Two functions will be tested: preferential targeting to different cellular domains and differential modulation by second messenger systems. These studies will contribute to our understanding of the molecular components and cellular regulation of Na currents. They also will provide an important foundation for understanding human neural and muscular diseases. Known mutations in the human adult skeletal muscle NaCh gene produce hyperexcitability and sometimes temporary paralysis. It is expected that mutations also occur in the other NaCh genes, most of which are expressed in the nervous system.