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https://www.readbyqxmd.com/read/28723241/the-effects-of-stretch-activation-on-ionic-selectivity-of-the-trek-2-k2p-k-channel
#1
Ehsan Nematian-Ardestani, Viwan Jarerattanachat, Prafulla Aryal, Mark S P Sansom, Stephen J Tucker
The TREK-2 (KCNK10) K2P potassium channel can be regulated by variety of polymodal stimuli including pressure. In a recent study, we demonstrated that this mechanosensitive K(+) channel responds to changes in membrane tension by undergoing a major structural change from its 'down' state to the more expanded 'up' state conformation. These changes are mostly restricted to the lower part of the protein within the bilayer, but are allosterically coupled to the primary gating mechanism located within the selectivity filter...
July 19, 2017: Channels
https://www.readbyqxmd.com/read/28698554/chondroprotection-by-urocortin-involves-blockade-of-the-mechanosensitive-ion-channel-piezo1
#2
K M Lawrence, R C Jones, T R Jackson, R L Baylie, B Abbott, B Bruhn-Olszewska, T N Board, I C Locke, S M Richardson, P A Townsend
Osteoarthritis (OA) is characterised by progressive destruction of articular cartilage and chondrocyte cell death. Here, we show the expression of the endogenous peptide urocortin1 (Ucn1) and two receptor subtypes, CRF-R1 and CRF-R2, in primary human articular chondrocytes (AC) and demonstrate its role as an autocrine/paracrine pro-survival factor. This effect could only be removed using the CRF-R1 selective antagonist CP-154526, suggesting Ucn1 acts through CRF-R1 when promoting chondrocyte survival. This cell death was characterised by an increase in p53 expression, and cleavage of caspase 9 and 3...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698214/papers-of-note-in-nature547-7661
#3
Annalisa M VanHook
This week's articles highlight progress in predicting T cell receptor specificity; an evolutionarily ancient form of antiviral defense; a mechanism of chemotherapy-induced cell death; metabolic rewiring in cancer cells; and structural insights into activation of a GPCR and of a mechanosensitive ion channel.
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28693035/k2p2-1-trek-1-activator-complexes-reveal-a-cryptic-selectivity-filter-binding-site
#4
Marco Lolicato, Cristina Arrigoni, Takahiro Mori, Yoko Sekioka, Clifford Bryant, Kimberly A Clark, Daniel L Minor
Polymodal thermo- and mechanosensitive two-pore domain potassium (K2P) channels of the TREK subfamily generate 'leak' currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses. These dimeric voltage-gated ion channel (VGIC) superfamily members have a unique topology comprising two pore-forming regions per subunit. In contrast to other potassium channels, K2P channels use a selectivity filter 'C-type' gate as the principal gating site...
July 10, 2017: Nature
https://www.readbyqxmd.com/read/28687864/stressed-podocytes-mechanical-forces-sensors-signaling-and-response
#5
REVIEW
Karlhans Endlich, Felix Kliewe, Nicole Endlich
Increased glomerular capillary pressure (glomerular hypertension) and increased glomerular filtration rate (glomerular hyperfiltration) have been proven to cause glomerulosclerosis in animal models and are likely to be operative in patients. Since podocytes cover the glomerular basement membrane, they are exposed to tensile stress due to circumferential wall tension and to fluid shear stress arising from filtrate flow through the narrow filtration slits and through Bowman's space. In vitro evidence documents that podocytes respond to tensile stress as well as to fluid shear stress...
July 7, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28678646/pain-areas-and-mechanosensitivity-in-patients-with-chronic-pelvic-pain-syndrome-a-controlled-clinical-investigation
#6
Jörgen Quaghebeur, Jean-Jacques Wyndaele, Stefan De Wachter
OBJECTIVE: A thorough clinical assessment including physical examination is crucial in a diagnostic work-up, including in patients with chronic pelvic pain syndrome (CPPS). This study investigated the prevalence of pain areas and the mechanosensitivity of peripheral nerves in patients with CPPS and compared the findings with a healthy control group. MATERIALS AND METHODS: Healthy volunteers and patients diagnosed with CPPS were assessed with physical examinations and neurodynamic testing...
July 5, 2017: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/28667050/regional-heterogeneity-in-the-mechanisms-of-myogenic-tone-in-hamster-arterioles
#7
William F Jackson, Erika M Boerman
Myogenic tone is an important feature of arterioles and resistance arteries, but the mechanisms responsible for this hallmark characteristic remain unclear. We utilized pharmacological inhibitors to compare the roles played by phospholipase C (PLC; 10 μM U73122), inositol 1,4,5 trisphosphate receptors (IP3R; 100 μM 2-Aminoethoxydiphenylborane, 2-APB), protein kinase C (PKC; 10μM Bisindolylmaleimide I), angiotensin II type 1 receptors (AT1R; 1μM losartan), Rho-kinase (10nM-30μM Y27632 or 300nM H1152), stretch-activated ion channels (10nM-1μM Gd(3+) or 5μM spider venom toxin GsMTx-4) and L-type voltage-gated Ca(2+) channels (0...
June 30, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28649635/gravireceptors-in-eukaryotes-a-comparison-of-case-studies-on-the-cellular-level
#8
Donat-P Häder, Markus Braun, Daniela Grimm, Ruth Hemmersbach
We have selected five evolutionary very different biological systems ranging from unicellular protists via algae and higher plants to human cells showing responses to the gravity vector of the Earth in order to compare their graviperception mechanisms. All these systems use a mass, which may either by a heavy statolith or the whole content of the cell heavier than the surrounding medium to operate on a gravireceptor either by exerting pressure or by pulling on a cytoskeletal element. In many cases the receptor seems to be a mechanosensitive ion channel activated by the gravitational force which allows a gated ion flux across the membrane when activated...
2017: NPJ Microgravity
https://www.readbyqxmd.com/read/28647645/adding-dimension-to-cellular-mechanotransduction-advances-in-biomedical-engineering-of-multiaxial-cell-stretch-systems-and-their-application-to-cardiovascular-biomechanics-and-mechano-signaling
#9
REVIEW
O Friedrich, D Schneidereit, Y A Nikolaev, V Nikolova-Krstevski, S Schürmann, A Wirth-Hücking, A L Merten, D Fatkin, B Martinac
Hollow organs (e.g. heart) experience pressure-induced mechanical wall stress sensed by molecular mechano-biosensors, including mechanosensitive ion channels, to translate into intracellular signaling. For direct mechanistic studies, stretch devices to apply defined extensions to cells adhered to elastomeric membranes have stimulated mechanotransduction research. However, most engineered systems only exploit unilateral cellular stretch. In addition, it is often taken for granted that stretch applied by hardware translates 1:1 to the cell membrane...
June 21, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28636944/transduction-of-repetitive-mechanical-stimuli-by-piezo1-and-piezo2-ion-channels
#10
Amanda H Lewis, Alisa F Cui, Malcolm F McDonald, Jörg Grandl
Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636818/critical-temperature-of-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine-monolayers-and-its-possible-biological-relevance
#11
Jordi H Borrell, Òscar Domènech
Because transmembrane proteins (TMPs) can be obtained with sufficient purity for X-ray diffraction studies more frequently than decades ago, their mechanisms of action may now be elucidated. One of the pending issues is the actual interplay between transmembrane proteins and membrane lipids. There is strong evidence of the involvement of specific lipids with some membrane proteins, such as the potassium crystallographically sited activation channel (KcsA) of Streptomyces lividans and the secondary transporter of lactose LacY of Escherichia coli, the activities of which are associated with the presence of anionic phospholipids such as the phosphatidylglycerol (PG) and phosphatidyethanolamine (PE), respectively...
July 5, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28627381/mechanosensing-in-hypothalamic-osmosensory-neurons
#12
REVIEW
Masha Prager-Khoutorsky
Osmosensory neurons are specialized cells activated by increases in blood osmolality to trigger thirst, secretion of the antidiuretic hormone vasopressin, and elevated sympathetic tone during dehydration. In addition to multiple extrinsic factors modulating their activity, osmosensory neurons are intrinsically osmosensitive, as they are activated by increased osmolality in the absence of neighboring cells or synaptic contacts. This intrinsic osmosensitivity is a mechanical process associated with osmolality-induced changes in cell volume...
June 13, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28606925/polarity-of-varicosity-initiation-in-central-neuron-mechanosensation
#13
Yuanzheng Gu, Peter Jukkola, Qian Wang, Thomas Esparza, Yi Zhao, David Brody, Chen Gu
Little is known about mechanical regulation of morphological and functional polarity of central neurons. In this study, we report that mechanical stress specifically induces varicosities in the axons but not the dendrites of central neurons by activating TRPV4, a Ca(2+)/Na(+)-permeable mechanosensitive channel. This process is unexpectedly rapid and reversible, consistent with the formation of axonal varicosities in vivo induced by mechanical impact in a mouse model of mild traumatic brain injury. In contrast, prolonged stimulation of glutamate receptors induces varicosities in dendrites but not in axons...
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28527849/role-of-piezo-channels-in-ultrasound-stimulated-dental-stem-cells
#14
Qianhua Gao, Paul R Cooper, A Damien Walmsley, Ben A Scheven
INTRODUCTION: Piezo1 and Piezo2 are mechanosensitive membrane ion channels. We hypothesized that Piezo proteins may play a role in transducing ultrasound-associated mechanical signals and activate downstream mitogen-activated protein kinase (MAPK) signaling processes in dental cells. In this study, the expression and role of Piezo channels were investigated in dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) after treatment with low-intensity pulsed ultrasound (LIPUS)...
May 17, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28526353/stretch-activated-two-pore-domain-k2p-potassium-channels-in-the-heart-focus-on-atrial-fibrillation-and-heart-failure
#15
Constanze Schmidt, Felix Wiedmann, Stefan M Kallenberger, Antonius Ratte, Jan S Schulte, Beatrix Scholz, Frank Ulrich Müller, Niels Voigt, Maria-Patapia Zafeiriou, Joachim R Ehrlich, Ursula Tochtermann, Gábor Veres, Arjang Ruhparwar, Matthias Karck, Hugo A Katus, Dierk Thomas
Two-pore-domain potassium (K2P) channels modulate cellular excitability. The significance of stretch-activated cardiac K2P channels (K2P2.1, TREK-1, KCNK2; K2P4.1, TRAAK, KCNK4; K2P10.1, TREK-2, KCNK10) in heart disease has not been elucidated in detail. The aim of this work was to assess expression and remodeling of mechanosensitive K2P channels in atrial fibrillation (AF) and heart failure (HF) patients in comparison to murine models. Cardiac K2P channel levels were quantified in atrial (A) and ventricular (V) tissue obtained from patients undergoing open heart surgery...
May 16, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28524182/cell-sized-mechanosensitive-and-biosensing-compartment-programmed-with-dna
#16
Sagardip Majumder, Jonathan Garamella, Ying-Lin Wang, Maxwell DeNies, Vincent Noireaux, Allen P Liu
The bottom-up construction of cell-sized compartments programmed with DNA that are capable of sensing the chemical and physical environment remains challenging in synthetic cell engineering. Here, we construct mechanosensitive liposomes with biosensing capability by expressing the E. coli channel MscL and a calcium biosensor using cell-free expression.
June 29, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28523001/the-role-of-transient-receptor-potential-vanilloid-4-in-pulmonary-inflammatory-diseases
#17
REVIEW
Rachel G Scheraga, Brian D Southern, Lisa M Grove, Mitchell A Olman
Ion channels/pumps are essential regulators of organ homeostasis and disease. In the present review, we discuss the role of the mechanosensitive cation channel, transient receptor potential vanilloid 4 (TRPV4), in cytokine secretion and pulmonary inflammatory diseases such as asthma, cystic fibrosis (CF), and acute lung injury/acute respiratory distress syndrome (ARDS). TRPV4 has been shown to play a role in lung diseases associated with lung parenchymal stretch or stiffness. TRPV4 indirectly mediates hypotonicity-induced smooth muscle contraction and airway remodeling in asthma...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28502667/mechanosensitivity-from-aristotle-s-sense-of-touch-to-cardiac-mechano-electric-coupling
#18
REVIEW
Johann P Kuhtz-Buschbeck, Jochen Schaefer, Nicolaus Wilder
Scientific interest in mechanosensation likely commenced with Aristotle's description of the sense of touch in his treatise de Anima [On the Soul]. Considering touch as a vital sense distributed over the whole body, the philosopher outlined a "physiological concept" at the macro-level already 2400 years ago. From this starting point, we outline the onset of modern sensory physiology during the early 19th century. Physiologists distinguished between outer and inner senses at that time, without, however, referring to specific receptors or nerves...
May 11, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28495756/cystic-fibrosis-transmembrane-conductance-regulator-mediates-tenogenic-differentiation-of-tendon-derived-stem-cells-and-tendon-repair-accelerating-tendon-injury-healing-by-intervening-in-its-downstream-signaling
#19
Yang Liu, Jia Xu, Liangliang Xu, Tianyi Wu, Yuxin Sun, Yuk-Wai Lee, Bin Wang, Hsiao-Chang Chan, Xiaohua Jiang, Jinfang Zhang, Gang Li
Tendons are a mechanosensitive tissue, which enables them to transmit to bone forces that are derived from muscle. Patients with tendon injuries, such as tendinopathy or tendon rupture, were often observed with matrix degeneration, and the healing of tendon injuries remains a challenge as a result of the limited understanding of tendon biology. Our study demonstrates that the stretch-mediated activation channel, cystic fibrosis transmembrane conductance regulator (CFTR), was up-regulated in tendon-derived stem cells (TDSCs) during tenogenic differentiation under mechanical stretching...
May 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28475214/the-angiotensin-ii-receptor-type-1b-is-the-primary-sensor-of-intraluminal-pressure-in-cerebral-artery-smooth-muscle-cells
#20
Paulo W Pires, Eun-A Ko, Harry A T Pritchard, Michael Rudokas, Evan Yamasaki, Scott Earley
The angiotensin II receptor type 1b (AT1 Rb ) is the primary sensor of intraluminal pressure in cerebral arteries. Pressure or membrane-stretch induced stimulation of AT1 Rb activates the TRPM4 channel and results in inward transient cation currents that depolarize smooth muscle cells, leading to vasoconstriction. Activation of either AT1 Ra or AT1 Rb with angiotensin II stimulates TRPM4 currents in cerebral artery myocytes and vasoconstriction of cerebral arteries. The expression of AT1 Rb mRNA is ∼30-fold higher than AT1 Ra in whole cerebral arteries and ∼45-fold higher in isolated cerebral artery smooth muscle cells...
July 15, 2017: Journal of Physiology
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