Transmural pressure and shear stress are mechanical forces that profoundly affect the smooth muscle cells (SMCs) comprising the vascular wall and the endothelial cells (ECs) lining the lumen. Pressure and flow are detected by mechanosensors in these cells and translated into appropriate responses to regulate blood pressure and flow. This review focuses on the role of the transient receptor potential (TRP) superfamily of cation channels in this process. We discuss how specific members of the TRP superfamily (TRPC6, TRPM4, TRPV1, TRPV4, and TRPP1) regulate the resting membrane and intracellular Ca2+ levels in SMCs and ECs to promote changes in vascular tone in response to intraluminal pressure and shear stress. Although TRP channels participate in vascular mechanotransduction, little evidence supports their intrinsic mechanosensitivity. Therefore, we also examine the evidence exploring the force-sensitive signal transduction pathways acting upstream of vascular TRP channels. Understanding the interplay between mechanosensors, force-induced signaling cascades, and TRP channels holds promise for the development of targeted therapies for diseases caused by vascular dysfunction.
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http://dx.doi.org/10.1093/ajh/hpae134 | DOI Listing |
Bioessays
December 2024
Section of Sensory Physiology, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
In this review, we introduce the concept of "dual thermosensing mechanisms," highlighting the functional collaboration between G protein-coupled receptors (GPCRs) and transient receptor potential (TRP) channels that enable sophisticated cellular thermal responsiveness. GPCRs have been implicated in thermosensory processes, with recent findings identifying several candidates across species, including mammals, fruit flies, and nematodes. In many cases, these GPCRs work in conjunction with another class of thermosensors, TRP channels, offering insights into the complex mechanisms underlying thermosensory signaling.
View Article and Find Full Text PDFBiophys J
December 2024
I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, St. Petersburg, Russia; Department of Biochemistry and Biomedical Sciences, Master University, Hamilton, Canada. Electronic address:
Despite their large functional diversity and poor sequence similarity, tetrameric and pseudo-tetrameric potassium, sodium, calcium and cyclic-nucleotide gated channels, as well as two-pore channels, transient receptor potential channels and ionotropic glutamate receptors share a common folding pattern of the transmembrane (TM) helices in the pore-forming domain. In each subunit or repeat, the pore domain has two TM helices connected by a membrane-reentering P-loop. The P-loop includes a membrane-descending helix, P1, which is structurally the most conserved element of these channels, and residues that contribute to the selectivity-filter region at the constriction of the ion-permeating pathway.
View Article and Find Full Text PDFJ Neuroinflammation
December 2024
Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands.
Microvascular brain endothelial cells tightly limit the entry of blood components and peripheral cells into the brain by forming the blood-brain barrier (BBB). The BBB is regulated by a cascade of mechanical and chemical signals including shear stress and elasticity of the adjacent endothelial basement membrane (BM). During physiological aging, but especially in neurological diseases including multiple sclerosis (MS), stroke, small vessel disease, and Alzheimer's disease (AD), the BBB is exposed to inflammation, rigidity changes of the BM, and disturbed cerebral blood flow (CBF).
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China.
Mechanical asphyxia presents a challenging diagnostic issue in forensic medicine due to its often covert nature, and the signs visible during an autopsy are usually not specific. Despite some progress in understanding hypoxia's effects, traditional methods' inherent limitations might overlook new biomarkers in mechanical asphyxia. This study employed 4D-DIA proteomics to explore the protein expression profiles of cardiac samples under conditions of mechanical asphyxia.
View Article and Find Full Text PDFFront Cell Dev Biol
November 2024
Department of Pharmacology and Pharmacotherapy, Medical School and Centre for Neuroscience, University of Pécs, Pécs, Hungary.
Transient Receptor Potential (TRP) ion channels like Vanilloid 1 (TRPV1) and Melastatin 3 (TRPM3) are nonselective cation channels expressed in primary sensory neurons and peripheral nerve endings, which are located in cholesterol- and sphingolipid-rich membrane lipid raft regions and have important roles in pain processing. Besides TRP ion channels a wide variety of voltage-gated ion channels were also described in the membrane raft regions of neuronal cells. Here we investigated the effects of lipid raft disruption by methyl-beta-cyclodextrin (MCD) and sphingomyelinase (SMase) on TRPV1, TRPM3 and voltage-gated L-type Ca channel activation in cultured trigeminal neurons and sensory nerve terminals of the trachea.
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