Mechanosensitive ion channels in intestinal homeostasis and disease

Mechanical deformation is integral to intestinal physiology, linking luminal transit to epithelial adaptation and motor control. These physical cues engage multiple mechanotransduction pathways that coordinate cellular adaptation and help preserve intestinal homeostasis. Inflammation, obstruction and matrix remodelling alter both the physical input and the state of the responding cell, allowing normally transient signals to persist or acquire pathological consequences. Ion channels act at several levels of this process. PIEZO1 and PIEZO2 provide a direct route for force-gated cation entry; mechanically gated two-pore-domain potassium channels can oppose depolarisation, and other conductances shape the conversion of mechanical signals into tissue responses. This review synthesises the current understanding of ion-channel mechanotransduction in intestinal physiology and disease. Studies have established the physiological importance of these pathways and are increasingly defining their contribution to disease, although their regulation in diseased tissue remains poorly understood.