Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University Baltimore, MD, USA.
Front Cell Neurosci. 2011 Oct 11;5:19. doi: 10.3389/fncel.2011.00019. eCollection 2011.
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 PO(2) 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.
颈动脉体（CB）是动脉缺氧的主要化学感受器器官。化学感觉球细胞（GCs）中 K 通道的抑制被认为是负责缺氧化学感受和/或 CB 的化学转导。在大鼠 CB 中已经确立了大电导钙激活钾（BK）通道的缺氧敏感性。我们之前的工作表明，BK 通道β2 亚基在 DBA/2J 小鼠的 CB 中比 A/J 小鼠表达更多。由于 DBA/2J 小鼠比 A/J 小鼠对缺氧更敏感，我们的一般假设是 BK 通道在小鼠 CB 对轻度缺氧的敏感性中起作用。我们对 CB 中 BK 通道的α、β2 和β4 亚基的基因表达进行了深入分析。我们发现，α 和β2 亚基在 DBA/2J 小鼠的 CB 中表达高于 A/J 小鼠。β4 亚基的表达没有差异。这些差异在相邻组织、颈上神经节和颈动脉中均未发现，表明这些差异是 CB 特异性的。此外，在使用未分离的 CB 的膜片钳实验中，研究了 GCs 中 BK 通道对轻度缺氧的敏感性。伊比替毒素显著抑制 DBA/2J 小鼠 GC 中的 K 电流，但不抑制 A/J 小鼠。当将 PO（2）降低到约 70mmHg 时，DBA/2J 小鼠 GC 中的 K 电流可逆转性降低，但 A/J 小鼠 GC 中的 K 电流不可逆转性降低。在伊比替毒素存在的情况下，轻度缺氧并未抑制两种品系的 K 电流。因此，数据表明 DBA/2J 小鼠 GC 中的 BK 通道对轻度缺氧敏感。CB 中 BK 通道β亚基的差异表达至少部分解释了这些小鼠品系之间不同的缺氧敏感性。
