studying-murine-small-bowel-mechanosensing-of-luminal-particulates

Studying Murine Small Bowel Mechanosensing of Luminal Particulates

Gastrointestinal (GI) motility is critical for normal digestion and absorption. In the small bowel, which absorbs nutrients, motility optimizes digestion ...

Mayo Clinic

 is expressed in cardiomyocytes and gastrointestinal (GI) smooth muscle cells (SMCs) as the voltage-gated mechanosensitive sodium channel Na1.5. The influx of Na through Na1.5 produces a fast depolarization in membrane potential, indispensable for electrical excitability in cardiomyocytes and important for electrical slow waves in GI smooth muscle. As such, abnormal Na1.5 voltage gating or mechanosensitivity may result in channelopathies.  mutation G615E - found separately in cases of acquired long-QT syndrome, sudden cardiac death, and irritable bowel syndrome - has a relatively minor effect on Na1.5 voltage gating. The aim of this study was to test whether G615E impacts mechanosensitivity. Mechanosensitivity of wild-type (WT) or G615E-Na1.5 in HEK-293 cells was examined by shear stress on voltage- or current-clamped whole cells or pressure on macroscopic patches. Unlike WT, voltage-clamped G615E-Na1.5 showed a loss in shear- and pressure-sensitivity of peak current yet a normal leftward shift in the voltage-dependence of activation. In current-clamp, shear stress led to a significant increase in firing spike frequency with a decrease in firing threshold for WT but not G615E-Na1.5. Our results show that the G615E mutation leads to functionally abnormal Na1.5 channels, which cause disruptions in mechanosensitivity and mechano-electrical feedback and suggest a potential contribution to smooth muscle pathophysiology.

 mutation G615E results in Na1.5 voltage-gated sodium channels with normal voltage-dependent function yet loss of mechanosensitivity.

TRPPing up bronchiectasis.

Facial aging is a multifactorial process that involves all tissues of the face, including skin, muscles, fat, ligaments, and bone. Whereas robust evidence is available for age-related changes of bone and facial fat, the influence of age on facial muscle activity is poorly understood.

Understanding Facial Muscle Aging: A Surface Electromyography Study.

Current options for the reduction of acne scarring (eg, ablative laser resurfacing) are associated with considerable side effects and limitations in terms of patient population. Percutaneous collagen induction via microneedling poses an alternative treatment method due to its low rates of reported adverse events and side effects.

Safety and efficacy of microneedling technology in the treatment of acne scars.

The gastrointestinal (GI) tract extracts nutrients from ingested meals while protecting the organism from infectious agents frequently present in meals. Consequently, most animals conduct the entire digestive process within the GI tract while keeping the luminal contents entirely outside the body, separated by the tightly sealed GI epithelium. Therefore, like the skin and oral cavity, the GI tract must sense the chemical and physical properties of the its external interface to optimize its function. Specialized sensory enteroendocrine cells (EECs) in GI epithelium interact intimately with luminal contents. A subpopulation of EECs express the mechanically gated ion channel Piezo2 and are developmentally and functionally like the skin's touch sensor- the Merkel cell. We hypothesized that Piezo2+ EECs endow the gut with intrinsic tactile sensitivity.

Specialized Mechanosensory Epithelial Cells in Mouse Gut Intrinsic Tactile Sensitivity.

The primary function of the gut is to procure nutrients. Synchronized mechanical activities underlie nearly all its endeavours. Coordination of mechanical activities depends on sensing of the mechanical forces, in a process called mechanosensation. The gut has a range of mechanosensory cells. They function either as specialized mechanoreceptors, which convert mechanical stimuli into coordinated physiological responses at the organ level, or as non-specialized mechanosensory cells that adjust their function based on the mechanical state of their environment. All major cell types in the gastrointestinal tract contain subpopulations that act as specialized mechanoreceptors: epithelia, smooth muscle, neurons, immune cells, and others. These cells are tuned to the physical properties of the surrounding tissue, so they can discriminate mechanical stimuli from the baseline mechanical state. The importance of gastrointestinal mechanosensation has long been recognized, but the latest discoveries of molecular identities of mechanosensors and technical advances that resolve the relevant circuitry have poised the field to make important intellectual leaps. This Review describes the mechanical factors relevant for normal function, as well as the molecules, cells and circuits involved in gastrointestinal mechanosensing. It concludes by outlining important unanswered questions in gastrointestinal mechanosensing.

Gut feelings: mechanosensing in the gastrointestinal tract.

With an increasing demand of aesthetic soft-tissue filler treatments, the occurrence of adverse events rises likewise. An optimized injection algorithm adapted to product characteristics (eg, rheology) of the soft-tissue filler is crucial in order to ensure satisfying clinical outcomes and high patient safety.

Arnaldo Mercado-Perez

Enteric NeuroScience Program (ENSP),
Division of Gastroenterology & Hepatology,
Department of Medicine,
Medical Scientist Training Program (MSTP),
Enteric NeuroScience Program (ENSP), Division of Gastroenterology & Hepatology, Department of Medicine

Mayo Clinic

Studying Murine Small Bowel Mechanosensing of Luminal Particulates