TRPV4 activation by thermal and mechanical stimuli in disease progression

Body temperature is an important determinant in regulating the activities of animals. In humans, a mild 0.5 °C hyperthermia can cause headaches, demonstrating that the maintenance of normal body temperature is a key for our health. In a more extreme example, accidental acute hypothermia can lead to severe shivering, loss of consciousness, or death, although the details of these mechanisms are poorly understood. We previously found that the TRPV4 ion channel is constitutively activated by normal body temperature. The activation threshold of TRPV4 is >34 °C in the brain, which enables TRPV4 to convert thermal information into cellular signaling. Here we review the data which describe how the deletion of TRPV4 evokes abnormal behavior in mice. These studies demonstrate that the maintenance of body temperature and the sensory system for detecting body temperature, such as via TRPV4, are critical components for normal cellular function. Moreover, abnormal TRPV4 activation exacerbates cell death, epilepsy, stroke, brain edema, or cardiac fibroblast activity. In this review, we also summarize the findings related to TRPV4 and disease.