Wilson S M, Toth P T, Oh S B, Gillard S E, Volsen S, Ren D, Philipson L H, Lee E C, Fletcher C F, Tessarollo L, Copeland N G, Jenkins N A, Miller R J
Mouse Cancer Genetics Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
J Neurosci. 2000 Dec 1;20(23):8566-71. doi: 10.1523/JNEUROSCI.20-23-08566.2000.
It has been hypothesized that R-type Ca currents result from the expression of the alpha(1E) gene. To test this hypothesis we examined the properties of voltage-dependent Ca channels in mice in which the alpha(1E) Ca channel subunit had been deleted. Application of omega-conotoxin GVIA, omega-agatoxin IVA, and nimodipine to cultured cerebellar granule neurons from wild-type mice inhibited components of the whole-cell Ba current, leaving a "residual" R current with an amplitude of approximately 30% of the total Ba current. A minor portion of this R current was inhibited by the alpha(1E)-selective toxin SNX-482, indicating that it resulted from the expression of alpha(1E). However, the majority of the R current was not inhibited by SNX-482. The SNX-482-sensitive portion of the granule cell R current was absent from alpha(1E) knock-out mice. We also identified a subpopulation of dorsal root ganglion (DRG) neurons from wild-type mice that expressed an SNX-482-sensitive component of the R current. However as with granule cells, most of the DRG R current was not blocked by SNX-482. We conclude that there exists a component of the R current that results from the expression of the alpha(1E) Ca channel subunit but that the majority of R currents must result from the expression of other Ca channel alpha subunits.
据推测，R型钙电流是由α(1E)基因的表达产生的。为了验证这一假设，我们研究了α(1E)钙通道亚基已被敲除的小鼠中电压依赖性钙通道的特性。将ω-芋螺毒素GVIA、ω-蜘蛛毒素IVA和尼莫地平应用于野生型小鼠培养的小脑颗粒神经元，可抑制全细胞钡电流的成分，留下一个“残余”R电流，其幅度约为总钡电流的30%。该R电流的一小部分被α(1E)选择性毒素SNX-482抑制，表明它是由α(1E)的表达产生的。然而，大部分R电流不受SNX-482抑制。α(1E)基因敲除小鼠的颗粒细胞R电流中不存在对SNX-482敏感的部分。我们还从小鼠的野生型背根神经节（DRG）神经元中鉴定出一个亚群，其表达R电流的SNX-482敏感成分。然而，与颗粒细胞一样，大多数DRG的R电流不受SNX-482阻断。我们得出结论，存在一部分R电流是由α(1E)钙通道亚基的表达产生的，但大多数R电流必定是由其他钙通道α亚基的表达产生的。
