Mechanosensitive Piezo Channels in the Gastrointestinal Tract

Abstract

Sensation of mechanical forces is critical for normal function of the gastrointestinal (GI) tract and abnormalities in mechanosensation are linked to GI pathologies. In the GI tract there are several mechanosensitive cell types—epithelial enterochromaffin cells, intrinsic and extrinsic enteric neurons, smooth muscle cells and interstitial cells of Cajal. These cells use mechanosensitive ion channels that respond to mechanical forces by altering transmembrane ionic currents in a process called mechanoelectrical coupling. Several mechanosensitive ionic conductances have been identified in the mechano-sensory GI cells, ranging from mechanosensitive voltage-gated sodium and calcium channels to the mechanogated ion channels, such as the two-pore domain potassium channels K2P (TREK-1) and nonselective cation channels from the transient receptor potential family. The recently discovered Piezo channels are increasingly recognized as significant contributors to cellular mechanosensitivity. Piezo1 and Piezo2 are nonselective cationic ion channels that are directly activated by mechanical forces and have well-defined biophysical and pharmacologic properties. The role of Piezo channels in the GI epithelium is currently under investigation and their role in the smooth muscle syncytium and enteric neurons is still not known. In this review, we outline the current state of knowledge on mechanosensitive ion channels in the GI tract, with a focus on the known and potential functions of the Piezo channels.

The enteric nervous system of the human and mouse colon at a single-cell resolution

“…5b), suggesting they have the capacity to directly sense distention. Previous studies reported Piezo1 expression in the ENS (78,79), which our atlas allows us to map to specific subsets. This refinement raises the hypothesis that peristalsis is at least partially driven by distention, specifically via motor neuron depolarization through Piezo1.…”

Stress–strain analysis of duodenal contractility in response to flow and ramp distension in rabbits fed low‐fiber diet

“…This indicates that duodenal sensitivity to distension‐induced contraction in rabbits on long‐term low‐fiber diet decreased. It is well known that the gastrointestinal tract contains intrinsic and extrinsic enteric neurons, smooth muscle cells, and interstitial cells of Cajal (ICC), which respond to mechanical deformations by altering transmembrane ionic currents in a process called mechanoelectrical coupling . It has been demonstrated that factors such as aging and diabetes change the mechanosensitivity.…”

Voltage‐gated sodium channels: (NaV)igating the field to determine their contribution to visceral nociception

“…To encode for such wide‐ranging stimuli, visceral organs rely on an array of stimuli‐activated primary ‘sentinel’ transducers, including transient receptor potential (TRP) channels, acid‐sensing ion channels (ASIC), mechanosensitive two‐pore domain K (K2P) channels and Piezo channels (Grundy, ; Brierley, ; Christianson & Davis, ; La & Gebhart, ; Brierley, ; Alcaino et al . ). Furthermore, primary transducers and ion channels involved in sensory signalling can be modulated and controlled by G‐protein coupled receptors (GPCRs) and regulators of GPCR signalling proteins, in response to endogenous mediators (Geppetti et al .…”