Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064-3095, USA.
Department of Cell and Systems Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, 807-8555, Japan.
Biochem Biophys Res Commun. 2023 Feb 19;645:17-23. doi: 10.1016/j.bbrc.2023.01.025. Epub 2023 Jan 11.
Adrenal medullary chromaffin (AMC) cells in the perinatal period and carotid body glomus cells after birth respond to hypoxia with catecholamine secretion. The hypoxia detection mechanism in such O-sensitive cells is still not well defined. One hypothesis is that a decrease in cellular ATP may be involved in the hypoxia detection. This idea is based on ATP dependence of TASK channel activity that regulates the resting membrane potential and is suppressed by hypoxia in glomus cells. Mitochondrial ATPase inhibitor factor-1 (IF), a physiological regulator of ATP synthase, helps prevent ATP hydrolysis under hypoxic conditions. In cells where IF expression is high, exposure to hypoxia is expected to have no effect on TASK channel activity. This possibility was electrophysiologically and immunocytochemically explored. Single channel recordings revealed that 36-pS TASK3-like channels contribute to the resting membrane potential in young rat adrenal cortical (AC) cells. TASK3-like channel activity in a cell-attached patch was not affected by bath application of mitochondrial inhibitors. Consistent with this finding, IF-like immunoreactive material was well expressed in rat AC cells. In further support of our hypothesis, IF-like immunoreactive material was well expressed in adult rat AMC cells that are known to be hypoxia-insensitive and minimally expressed in newborn AMC cells that are hypoxia-sensitive. These results provide evidence for the functional relevance of IF expression in excitability in O-sensitive cells in response to mitochondrial inhibition.
围生期肾上腺髓质嗜铬（AMC）细胞和出生后颈动脉体球细胞在缺氧时会分泌儿茶酚胺。这种 O 敏感细胞中的缺氧检测机制仍未得到很好的定义。一种假设是细胞内 ATP 的减少可能参与了缺氧检测。这个想法基于 TASK 通道活性对 ATP 的依赖性，TASK 通道活性调节静息膜电位，并在球细胞中被缺氧抑制。线粒体 ATP 酶抑制剂因子-1（IF）是 ATP 合酶的生理调节剂，有助于在缺氧条件下防止 ATP 水解。在 IF 表达水平较高的细胞中，预计缺氧对 TASK 通道活性没有影响。这种可能性在电生理学和免疫细胞化学上进行了探索。单通道记录显示，36-pS TASK3 样通道有助于年轻大鼠肾上腺皮质（AC）细胞的静息膜电位。细胞贴附式斑块中的 TASK3 样通道活性不受线粒体抑制剂浴液应用的影响。与这一发现一致，IF 样免疫反应物质在大鼠 AC 细胞中表达良好。进一步支持我们的假设是，已知对缺氧不敏感的成年大鼠 AMC 细胞中 IF 样免疫反应物质表达良好，而对缺氧敏感的新生 AMC 细胞中 IF 样免疫反应物质表达较少。这些结果为 IF 表达在对线粒体抑制的 O 敏感细胞的兴奋性中的功能相关性提供了证据。
