Redox-sensitive transient receptor potential channels in oxygen sensing and adaptation

Regulation of ion channels is central to the mechanisms that underlie immediate acute physiological responses to changes in the availability of molecular oxygen (O(2)). A group of cation-permeable channels that are formed by transient receptor potential (TRP) proteins have been characterized as exquisite sensors of redox reactive species and as efficient actuators of electric/ionic signals in vivo. In this review, we first discuss how redox-sensitive TRP channels such as TRPA1 have recently emerged as sensors of the relatively inert oxidant O(2). With regard to the physiological significance of O(2) sensor TRP channels, vagal TRPA1 channels are mainly discussed with respect to their role in respiratory regulation in comparison with canonical pathways in glomus cells of the carotid body, which is a well-established O(2)-sensing organ. TRPM7 channels are discussed regarding hypoxia-sensing function in ischemic cell death. Also, ubiquitous expression of TRPA1 and TRPM7 together with their physiological relevance in the body is examined. Finally, based upon these studies on TRP channels, we propose a hypothesis of “O(2) remodeling.” The hypothesis is that cells detect deviation of O(2) availability from appropriate levels via sensors and adjust local O(2) environments in vivo by controlling supply and consumption of O(2) via pathways comprising cellular signals and transcription factors downstream of sensors, which consequently optimize physiological functions. This new insight into O(2) adaptation through ion channels, particularly TRPs, may foster a paradigm shift in our understanding in the biological significance of O(2).