Kvα1 channels in murine arterioles:: differential cellular expression and regulation of diameter

Kvα1 channels in murine arterioles:: differential cellular expression and regulation of diameter
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DOI:
10.1152/ajpheart.2001.281.3.h1057
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发表时间:
2001-09-01
影响因子:
4.8
通讯作者:
Beech, DJ
Beech, DJ
中科院分区:
医学2区
文献类型:
--
作者:
Cheong, A;Dedman, AM;Beech, DJ

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本研究的主要目的是揭示小鼠脑循环毛细血管前小动脉中电压门控K+通道(K(V)alpha1)亚基的细胞特异性表达模式和功能。K(V)alpha1用肽特异性抗体进行免疫荧光和Western blotting检测。K(V)1.2几乎完全定位于内皮细胞,而K(V)1.5则分散定位于支配小动脉的神经和神经末梢。K(V)1.5也特异定位于人脑脊膜的小动脉神经。K(V)1.5在平滑肌细胞中缺失。K(V)1.3、K(V)1.4和K(V)1.6定位于内皮细胞和平滑肌细胞,但K(V)1.4表达水平较低。K(V)1.1未表达。因此,我们发现不同细胞类型的动脉小动脉具有不同的K(V)alpha1生理表达谱,赋予细胞外和第二信使差异调节的可能性。此外,我们发现重组agitoxin-2和margatoxin是有效的血管收缩剂,这表明K(V)alpha1亚基在决定小动脉对血流的抵抗中起主要作用。
The primary objectives of this study were to reveal cell-specific expression patterns and functions of voltage-gated K+ channel (K(V)alpha1) subunits in precapillary arterioles of the murine cerebral circulation. K(V)alpha1 were detected using peptide-specific antibodies in immunofluorescence and Western blotting assays. K(V)1.2 was localized almost exclusively to endothelial cells, whereas K(V)1.5 was discretely localized to the nerves and nerve terminals that innervate the arterioles. K(V)1.5 also localized specifically to arteriolar nerves in human pial membrane. K(V)1.5 was notable for its absence from smooth muscle cells. K(V)1.3, K(V)1.4, and K(V)1.6 were localized to endothelial and smooth muscle cells, although K(V)1.4 had a low expression level. K(V)1.1 was not expressed. Therefore, we show that different cell types of pial arterioles have distinct physiological expression profiles of K(V)alpha1, conferring the possibility of differential modulation by extracellular and second messengers. Furthermore, we show recombinant agitoxin-2 and margatoxin are potent vasoconstrictors, suggesting that K(V)alpha1 subunits have a major function in determining arteriolar resistance to blood flow.