DISSECTING ROD CNG CHANNEL FUNCTION WITH PSEUDECHETOXIN

描述：环核苷酸门控离子通道首次发现于 视网膜杆，在那里它们产生细胞的电活动， 对光的反应。环核苷酸门控（CNG）通道的另一个成员 家族随后在嗅觉受体神经元中被发现。无论是 系统，CNG通道隐蔽刺激诱导的细胞内变化 将环核苷酸水平转化为膜电位的分级变化， 从而调节突触处神经递质的释放。CNG通道 在视网膜的双极细胞和神经节细胞以及海马神经元中也发现了 神经元，在那里它们可以改变突触强度以响应一氧化氮 线索最近，CNG通道已经在整个组织中被发现。 身体包括大脑、心脏、肝脏、肾脏和睾丸。CNG的作用 这些组织中的通道更具有推测性。缺乏具体 药理学工具使得很难明确地确定 CNG通道的生理作用。电压门控钠的特异性阻断剂， 钙和钾通道以及许多离子型神经递质受体 但CNG通道阻断剂缺乏。最近这 一名研究人员从澳大利亚的毒液中纯化出一种新的肽毒素。 棕色蛇，Pseudechis australis，它阻止电流通过CNG通道。 这种毒素被称为假黄毒素（PsTx），是一种高度碱性的24-kDa蛋白质。 当应用于含有以下物质的膜贴片的细胞外表面时， α-亚单位的杆通道，PsTx抑制电流与一个明显的 亲和力为100 nM。它甚至能更有效地阻断嗅觉 CNG通道的版本。研究人员现在建议研究 PsTx和CNG通道之间的相互作用， 电生理学方法。希望PsTx能成为一个有价值的 用于辨别视网膜中CNG通道的功能的药理学工具， 在整个身体。这些研究旨在更好地了解 CNG通道在健康和疾病的生理学，并将奠定基础， 药物设计的未来努力。

DESCRIPTION: Cyclic nucleotide-gated ion channels were first discovered in retinal rods where they generate the electrical activity of the cell in response to light. Another member of the cyclic nucleotide-gated (CNG) channel family was subsequently discovered in olfactory receptor neurons. In both systems, CNG channels covert stimulus-induced changes in the intracellular levels of cyclic nucleotides into graded changes in the membrane potential, thereby modulating the release of neurotransmitter at the synapse. CNG channels are also found in bipolar and ganglion cells of the retina and in hippocampal neurons where they may modify synaptic strength in response to nitric oxide cues. More recently, CNG channels have been found in tissues throughout the body including the brain, heart, live, kidneys, and testes. The role of the CNG channels in these tissues is more speculative. The lack of specific pharmacological tools has made it difficult to unambiguously determine the physiological role of CNG channels. Specific blockers of voltage-gated sodium, calcium and potassium channels and many ionotropic neurotransmitter receptors are available but blockers for CNG channels are scarce. Recently this investigator purified a novel peptide toxin from the venom of the Australian Brown snake, Pseudechis australis, which blocks current through CNG channels. This toxin, termed Pseudechetoxin (PsTx), is a highly basic 24-kDa protein. When applied to the extracellular face of membrane patches containing the alpha-subunit of the rod channel, PsTx inhibited current with an apparent affinity of 100 nM. It was even more effective at blocking the olfactory version of the CNG channel. The investigator now proposes to study the interaction between PsTx and CNG channels using molecular genetic and electrophysiological methods. It is hoped that PsTx will be a valuable pharmacological tool to discern the function of CNG channels in the retina and throughout the body. These studies aim to provide a better understanding of the physiology of CNG channels in health and disease and will lay a foundation for future endeavors in drug design.