Mechanotransduction in gastrointestinal smooth muscle cells: role of mechanosensitive ion channels

Abstract

Mechanosensation, the ability to properly sense mechanical stimuli and transduce them into physiologic responses, is an essential determinant of gastrointestinal (GI) function. Abnormalities in this process result in highly prevalent GI functional and motility disorders. In the GI tract, several cell types sense mechanical forces and transduce them into electrical signals, which elicit specific cellular responses. Some mechanosensitive cells like sensory neurons act as specialized mechanosensitive cells that detect forces and transduce signals into tissue-level physiologic reactions. Non-specialized mechanosensitive cells like smooth muscle cells (SMCs) adjust their function in response to forces. Mechanosensitive cells utilize various mechanoreceptors and mechanotransducers. Mechanoreceptors detect and convert force into electrical and biochemical signals, and mechanotransducers amplify and direct mechanoreceptor responses. Mechanoreceptors and mechanotransducers include ion channels, specialized cytoskeletal proteins, cell junction molecules, and G-protein coupled receptors. SMCs are particularly important due to their role as final effectors for motor function. Myogenic reflex-the ability of smooth muscle to contract in response to stretch rapidly-is a critical smooth muscle function. Such rapid mechanotransduction responses rely on mechano-gated and -sensitive ion channels, which alter their ion pores' opening in response to force, allowing fast electrical and Ca2+ responses. Though GI SMCs express a variety of such ion channels, their identities remain unknown. Recent advancements in electrophysiological, genetic, in vivo imaging, and multi-omic technologies broaden our understanding of how SMC mechano-gated and -sensitive ion channels regulate GI functions. This review discusses GI SMC mechanosensitivity's current developments with a particular emphasis on mechano-gated and -sensitive ion channels.

Capsaicin as an amphipathic modulator of NaV1.5 mechanosensitivity

“…The MS of voltage-gated ion channels contributes to a mechano-electrical feedback system that has important implications in organs with primarily mechanical functions [ 14 , 48 , 49 ]. Examples of such mechanically active organs include the heart and gut, where ion channels contribute to important physiologic functions [ 14 , 50 ]. In the human heart and gut, the voltage-gated sodium channel, Na V 1.5 serves as a key electrically excitable component in both the cardiac action potential and GI smooth muscle contraction [ 17 , 50 ].…”

“…Examples of such mechanically active organs include the heart and gut, where ion channels contribute to important physiologic functions [ 14 , 50 ]. In the human heart and gut, the voltage-gated sodium channel, Na V 1.5 serves as a key electrically excitable component in both the cardiac action potential and GI smooth muscle contraction [ 17 , 50 ]. Besides being voltage-gated, Na V 1.5 is mechanosensitive [ 37 ]; this property contributes to mechano-electrical feedback [ 49 ].…”

Association of Gastric Myoelectrical Activity With Ghrelin, Gastrin, and Irisin in Adults With Metabolically Healthy and Unhealthy Obesity

“…There is also a pacemaker, interstitial cells of Cajal (ICC), which generates slow-wave activity that spreads into the gastric wall ( Tse et al, 2016 ). The ICC also contains a voltage-gated L-type Ca 2+ channel which is activated at -60 mV in addition to mechanosensitive ion channels that respond to mechanically gated changes in ion channel currents leading to modulation of the electrical slow-wave of the ICC ( Kraichely and Farrugia, 2007 ; Joshi et al, 2021 ). Centrally, brain–stomach coupling is evident in humans ( Wang Y.…”

Mechanical forces directing intestinal form and function

“…Ingestion of food results in shear forces exerted on the epithelial surface as food particles flow through the lumen, and additionally increases peristaltic smooth muscle contractions that lead to mechanical distention and compression of the intestinal wall 85 . The ability of the intestine to sense and respond to these mechanical signals is critical for the regulation of intestinal digestive functions, including stimulation of peristaltic contractions and secretion of mucus and hormones 86,87 . These responses are in part mediated by mechanosensitive ion channel activation in sensory neurons that innervate the gastrointestinal tract 88,89 .…”