Differential Expression of Large-Conductance Ca-Activated K Channels in the Carotid Body between DBA/2J and A/J Strains of Mice.

Differential Expression of Large-Conductance Ca-Activated K Channels in the Carotid Body between DBA/2J and A/J Strains of Mice.
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DOI:
10.3389/fncel.2011.00019
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发表时间:
2011
影响因子:
5.3
通讯作者:
Shirahata M
Shirahata M
中科院分区:
医学2区
文献类型:
--
作者:
Otsubo T;Kostuk EW;Balbir A;Fujii K;Shirahata M

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颈动脉小体(CB)是动脉缺氧的主要化学感受器。化学感觉球状细胞(GCs)K通道的抑制被认为与CB的低氧化学接受和/或化学转导有关。大电导钙激活钾(BK)通道的低氧敏感性已在大鼠脐血中建立。我们以前的工作表明,BK通道β2亚基在Dba/2J小鼠的CB中的表达高于A/J小鼠。由于DBA/2J小鼠比A/J小鼠对低氧更敏感,我们的一般假设是BK通道在小鼠CB对轻度低氧的敏感性中起作用。我们对CB中α,β-2和β-4亚基BK通道的基因表达进行了有力的分析。结果发现,α和β-2亚基在DBA/2J小鼠脐带血中的表达高于A/J小鼠。β4亚单位表达差异无统计学意义。这些差异在邻近组织、颈上神经节和颈动脉中未见,提示这种差异是CB特有的。此外,使用未分离的CBS进行膜片钳实验,检测GCs的BK通道对轻度低氧的敏感性。伊贝类毒素对DBA/2J小鼠GCs钾电流有明显抑制作用,但对A/J小鼠无明显抑制作用。当氧分压降至70 毫米汞柱时,DBA/2J小鼠GC的K电流可逆地降低,而A/J小鼠则不能。在硫杆菌毒素存在的情况下,轻度低氧对两种菌株的钾电流均无抑制作用。提示DBA/2J小鼠GCs的BK通道对轻度低氧敏感。BK通道β亚基在CBS中的差异表达可能至少部分解释了这些小鼠品系对低氧的不同敏感性。
The carotid body (CB) is a primary chemosensory organ for arterial hypoxia. Inhibition of K channels in chemosensory glomus cells (GCs) are considered to be responsible for hypoxic chemoreception and/or chemotransduction of the CB. Hypoxic sensitivity of large-conductance calcium-activated K (BK) channels has been established in the rat CB. Our previous work has shown the BK channel β2 subunits are more expressed in the CB of the DBA/2J mouse than that of the A/J mouse. Because the DBA/2J mouse is more sensitive to hypoxia than the A/J mouse, our general hypothesis is that BK channels play a role in the sensitivity of the mouse CB to mild hypoxia. We performed vigorous analysis of the gene expression of α, β2, and β4 subunits of BK channels in the CB. We found that α and β2 subunits were expressed more in the CB of the DBA/2J mice than that of the A/J mice. No differences were found in the β4 subunit expression. These differences were not seen in the neighboring tissues, the superior cervical ganglion and the carotid artery, suggesting that the differences are CB specific. Further, the sensitivity of BK channels in GCs to mild hypoxia was examined in patch clamp experiments using undissociated CBs. Iberiotoxin significantly inhibited K current of GCs in the DBA/2J mice, but not in the A/J mice. When reducing PO2 to ∼70 mmHg, K current reversibly decreased in GCs of the DBA/2J, but not of the A/J mice. In the presence of iberiotoxin, mild hypoxia did not inhibit K current in either strains. Thus, the data suggest that BK channels in GCs of the DBA/2J mice are sensitive to mild hypoxia. Differential expression of BK channel β subunits in the CBs may, at least in part, explain the different hypoxic sensitivity in these mouse strains.
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发表时间: 1996-12-02
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影响因子: 2.9
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