Bourinet E, Zamponi G W, Stea A, Soong T W, Lewis B A, Jones L P, Yue D T, Snutch T P
Biotechnology Laboratory, University of British Columbia, Vancouver, Canada.
J Neurosci. 1996 Aug 15;16(16):4983-93. doi: 10.1523/JNEUROSCI.16-16-04983.1996.
The physiological and pharmacological properties of the alpha 1E calcium (Ca) channel subtype do not exactly match any of the established categories described for native neuronal Ca currents. Many of the key diagnostic features used to assign cloned Ca channels to their native counterparts, however, are dependent on a number of factors, including cellular environment, beta subunit coexpression, and modulation by second messengers and G-proteins. Here, by examining the intrinsic pore characteristics of a family of transiently expressed neuronal Ca channels, we demonstrate that the permeation properties of alpha 1E closely resemble those described for a subset of low-threshold Ca channels. The alpha 1A (P-/Q-type), alpha 1B (N-type), and alpha 1C (L-type) high-threshold Ca channels all exhibit larger whole-cell currents with barium (Ba) as the charge carrier as compared with Ca or strontium (Sr). In contrast, macroscopic alpha 1E currents are largest in Sr, followed by Ca and then Ba. The unique permeation properties of alpha 1E are maintained at the single-channel level, are independent of the nature of the expression system, and are not affected by coexpression of alpha 2 and beta subunits. Overall, the permeation characteristics of alpha 1E are distinct from those described for R-type currents and share some similarities with native low-threshold Ca channels.
α1E钙(Ca)通道亚型的生理和药理特性与已描述的天然神经元Ca电流的任何既定类别都不完全匹配。然而,用于将克隆的Ca通道与其天然对应物进行匹配的许多关键诊断特征取决于多种因素,包括细胞环境、β亚基共表达以及第二信使和G蛋白的调节。在这里,通过检查一组瞬时表达的神经元Ca通道的内在孔特性,我们证明α1E的通透特性与低阈值Ca通道子集所描述的特性非常相似。与Ca或锶(Sr)相比,α1A(P-/Q型)、α1B(N型)和α1C(L型)高阈值Ca通道在以钡(Ba)作为电荷载体时均表现出更大的全细胞电流。相比之下,宏观α1E电流在Sr中最大,其次是Ca,然后是Ba。α1E独特的通透特性在单通道水平上得以维持,与表达系统的性质无关,并且不受α2和β亚基共表达的影响。总体而言,α1E的通透特性与R型电流所描述的特性不同,并且与天然低阈值Ca通道有一些相似之处。