决定神经元钙通道差异受体调节的结构特征。
Structural features determining differential receptor regulation of neuronal Ca channels.
作者信息
Simen A A, Miller R J
机构信息
Department of Pharmacological and Physiological Sciences, Committee on Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
出版信息
J Neurosci. 1998 May 15;18(10):3689-98. doi: 10.1523/JNEUROSCI.18-10-03689.1998.
Abstract
Dihydropyridine-insensitive Ca channels are subject to direct receptor G-protein-mediated inhibition to differing extents. alpha1B channels are much more strongly modulated than alpha1E channels. To understand the structural basis for this difference, we have constructed and expressed various alpha1B and alpha1E chimeric Ca channels and examined their regulation by kappa-opioid receptors. Replacement of the first membrane-spanning domain of alpha1E with the corresponding region of alpha1B resulted in a chimeric Ca channel that was modulated by kappa-opioid receptors to a significantly greater extent than alpha1E. Transfer of the N terminus and I/II loop from alpha1B in addition to domain I resulted in a chimeric channel that was modulated to the same extent as alpha1B. Other regions of the molecule do not appear to contribute significantly to the degree of inhibition obtained, although the C terminus may contribute to facilitation.
摘要
二氢吡啶不敏感的钙通道在不同程度上受到直接受体G蛋白介导的抑制。α1B通道比α1E通道受到更强的调节。为了理解这种差异的结构基础，我们构建并表达了各种α1B和α1E嵌合钙通道，并研究了它们受κ-阿片受体的调节情况。用α1B的相应区域替换α1E的第一个跨膜结构域，产生了一种嵌合钙通道，其受κ-阿片受体的调节程度比α1E显著更高。除结构域I外，将α1B的N端和I/II环转移过来，产生了一种调节程度与α1B相同的嵌合通道。尽管C端可能有助于促进作用，但分子的其他区域似乎对所获得的抑制程度没有显著贡献。
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