Oxygen-dependent regulation of ion channels: acute responses, post-translational modification, and response to chronic hypoxia

Oxygen is a vital element for the survival of cells in multicellular aerobic organisms such as mammals. Lack of O2 availability caused by environmental or pathological conditions leads to hypoxia. Active oxygen distribution systems (pulmonary and circulatory) and their neural control mechanisms ensure that cells and tissues remain oxygenated. However, O2-carrying blood cells as well as immune and various parenchymal cells experience wide variations in partial pressure of oxygen (PO2) in vivo. Hence, the reactive modulation of the functions of the oxygen distribution systems and their ability to sense PO2 are critical. Elucidating the physiological responses of cells to variations in PO2 and determining the PO2-sensing mechanisms at the biomolecular level have attracted considerable research interest in the field of physiology. Herein, we review the current knowledge regarding ion channel–dependent oxygen sensing and associated signalling pathways in mammals. First, we present the recent findings on O2-sensing ion channels in representative chemoreceptor cells as well as in other types of cells such as immune cells. Furthermore, we highlight the transcriptional regulation of ion channels under chronic hypoxia and its physiological implications and summarize the findings of studies on the post-translational modification of ion channels under hypoxic or ischemic conditions.