Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile.
Respir Physiol Neurobiol. 2013 Feb 1;185(3):600-7. doi: 10.1016/j.resp.2012.11.015. Epub 2012 Dec 3.
Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to acute hypoxia. In spite of that, the primary molecular target of CIH in the CB remains unknown. A key step of the hypoxic response in the CB is the chemoreceptor cell depolarization elicited by the inhibition of K(+) channels. Thus, we tested the hypothesis that CIH potentiates the hypoxic-induced depolarization of rat CB chemoreceptor cells by enhancing the inhibition of a background K(+) TASK-like channel. Membrane potential, single channel and macroscopic currents were recorded in the presence of TEA and 4-aminopyridine in CB chemoreceptor cells isolated from adult rats exposed to CIH. The CIH treatment did not modify the resting membrane properties but the hypoxic-evoked depolarization increased by 2-fold. In addition, the hypoxic inhibition of the TASK-like channel current was larger and faster in glomus cells from CIH-treated animals. This novel effect of CIH may contribute to explain the enhancing effect of CIH on CB oxygen chemoreception.
慢性间歇性低氧(CIH)是阻塞性睡眠呼吸暂停的主要特征,增强了颈动脉体(CB)对急性低氧的化学感受反应。尽管如此,CB 中 CIH 的主要分子靶点仍不清楚。CB 中低氧反应的关键步骤是由 K(+)通道抑制引起的化学感受器细胞去极化。因此,我们假设 CIH 通过增强背景 K(+) TASK 样通道的抑制来增强大鼠 CB 化学感受器细胞缺氧诱导的去极化,从而检验了这一假设。在成年大鼠暴露于 CIH 条件下分离的 CB 化学感受器细胞中,使用 TEA 和 4-氨基吡啶记录膜电位、单通道和宏观电流。CIH 处理不改变静息膜特性,但缺氧引起的去极化增加了 2 倍。此外,CIH 处理动物的球细胞中 TASK 样通道电流的缺氧抑制更大且更快。CIH 的这种新作用可能有助于解释 CIH 对 CB 氧化学感受的增强作用。