Biological fundamental functional units of meridians: mechanosensitive ion channels

Meridians are central to the theory of Traditional Chinese Medicine (TCM), yet their biological essence remains elusive. Mechanosensitive ion channels (MS channels) respond to diverse physical stimuli, and their properties closely parallel the biophysical characteristics attributed to meridians. Here, we propose the hypothesis that MS channels serve as the fundamental biological functional units of meridians. To test this hypothesis, we systematically compared the properties of MS channels with those of meridians and utilized Zusanli (ST36) as a model to dissect the critical role of MS channels in mediating the complete signaling pathway of acupuncture—from local initiation and central integration to visceral effector responses. Furthermore, applying this hypothesis successfully addresses three major challenges in meridian research: (1) the efficacy of sham acupuncture, which arises from the ubiquitous distribution of MS channels and their response gradients; (2) variations in the pathways of propagated sensation along meridians, which result from MS channel activity being guided by anatomical networks and modulated by central processes; and, importantly, (3) the persistence of meridian function following organ transplantation, which can be coherently explained by a mechanism wherein systemic signals from the recipient remotely regulate MS channels on the cells of the transplanted organ, thereby providing a modern biological basis for the concept of “meridian transplantation.” This hypothesis provides a testable molecular framework for understanding the essence of meridians, bridging traditional functional descriptions with modern developmental biology, neuroscience, and cellular and molecular mechanisms.