Poulsen Asser Nyander, Wulf Helle, Hay-Schmidt Anders, Jansen-Olesen Inger, Olesen Jes, Klaerke Dan A
Department of Physiology and Biochemistry, IBHV, Faculty of Life Sciences, University of Copenhagen, Groennegaardsvej 7, 1870 Frederiksberg C, Denmark.
Biochim Biophys Acta. 2009 Feb;1788(2):380-9. doi: 10.1016/j.bbamem.2008.10.001. Epub 2008 Oct 18.
We investigated the expression of splice variants and beta-subunits of the BK channel (big conductance Ca2+-activated K+ channel, Slo1, MaxiK, KCa1.1) in rat cerebral blood vessels, meninges, trigeminal ganglion among other tissues. An alpha-subunit splice variant X1(+24) was found expressed (RT-PCR) in nervous tissue only where also the SS4(+81) variant was dominating with little expression of the short form SS4(0). SS4(+81) was present in some cerebral vessels too. The SS2(+174) variant (STREX) was found in both blood vessels and in nervous tissue. In situ hybridization data supported the finding of SS4(+81) and SS2(+174) in vascular smooth muscle and trigeminal ganglion. beta-subunits beta2 and beta4 showed high expression in brain and trigeminal ganglion and some in cerebral vessels while beta1 showed highest expression in blood vessels. beta3 was found only in testis and possibly brain. A novel splice variant X2(+92) was found, which generates a stop codon in the intracellular C-terminal part of the protein. This variant appears non-functional as a homomer but may modulate the function of other splice-variants when expressed in Xenopus oocytes. In conclusion a great number of splice variant and beta-subunit combinations likely exist, being differentially expressed among nervous and vascular tissues.
我们研究了大电导钙激活钾通道(BK通道,Slo1、MaxiK、KCa1.1)的剪接变体和β亚基在大鼠脑血管、脑膜、三叉神经节及其他组织中的表达情况。发现α亚基剪接变体X1(+24)仅在神经组织中表达(逆转录聚合酶链反应),在该组织中SS4(+81)变体也占主导地位,而短形式SS4(0)表达较少。SS4(+81)在一些脑血管中也有存在。SS2(+174)变体(STREX)在血管和神经组织中均有发现。原位杂交数据支持了在血管平滑肌和三叉神经节中发现SS4(+81)和SS2(+174)的结果。β亚基β2和β4在脑和三叉神经节中高表达,在一些脑血管中也有一定表达,而β1在血管中表达最高。β3仅在睾丸中发现,可能在脑中也有。发现了一种新的剪接变体X2(+92),它在蛋白质的细胞内C末端部分产生一个终止密码子。该变体作为同聚体似乎无功能,但当在非洲爪蟾卵母细胞中表达时可能调节其他剪接变体的功能。总之,可能存在大量的剪接变体和β亚基组合,它们在神经组织和血管组织中差异表达。