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Trimeric Scaffold Ligand-Gated Ion Channels
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Xiao-Na Yang, Si-Yu Wang, Jin Wang, Ye Yu
Precedent studies on the subunit stoichiometry of ASICs never cease to be questioned by results that ASICs should be a tetramer (36), which is identical to those of FaNaC and ENaC (37,38). Nine subunits appear as another stoichiometric mode of the DEG/ENaC superfamily (39–41). It was commonly accepted that a functional ASIC is organized as a trimer until the crystal structure of chicken ASIC1 (cASIC1) at the desensitized state was determined by Dr. Gouaux and colleagues in 2007 (42) (Figure 3.2A, left). This discrepancy also occurred on many membrane proteins; for example, the bacterial mechanosensitive ion channel MscL was firstly identified as a hexamer by chemical crosslinking (43), then was confirmed by X-ray crystallography as a pentamer (44). Similarly, although the majority of studies concerning P2X receptors concluded them as trimeric in formation, opinion by Kim et al. differed by presuming that the native assembling of P2X2 might be a tetramer (45), a prediction derived from the folding studies of the extracellular domain of P2X2. Ding et al. conjured the same result by evaluating the influence of Ca2+ on inactivation of P2X receptors (46). The crystal structure of zebra fish P2X4 (zfP2X4) determined by Gouaux et al. put this controversy to an end (47) (Figure 3.2B, left). The structure of cASIC and zfP2X4 indicate that three subunits of constituent formed a pseudo ternary symmetry by enclosing a central axis (48).
Structure and Function of Cartilage
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
Recently, primary cilium has come into focus as a mechanosensor of fluid flow. The primary cilium is a small membrane protrusion containing microtubules present on almost all vertebrate cells that can act as an “extracellular antenna” for detection of the external environment (Marshall and Nonaka 2006; Singla and Reiter 2006) (Figure 1.12). It also acts as a signaling center for sonic hedgehog (Shh), patched (PTC), and other molecules that can regulate cell survival, growth and differentiation, and tissue homeostasis (Christensen et al. 2008; Veland et al. 2009). For instance, in bone the primary cilium has been demonstrated to deflect under flow and to be independent of Ca2+ flux and stretch-activated ion channels in fluid flow-induced PGE2 release (Malone et al. 2007). Interestingly, in the endothelium of the kidney (Yoder 2007) or vascular system, the primary cilium appears to transduce fluid flow through an increase in intracellular Ca2+ (Van der Heiden et al. 2006). In the kidney, this has been linked to interactions between the primary cilium and polycystins 1 and 2 to form a mechanosensitive ion channel (Forman et al. 2005) (Figure 1.13). In chondrocytes, the length of the primary cilium may be regulated by mechanical loading (McGlashan et al. 2010).
CBF regulation in hypertension and Alzheimer’s disease
Published in Clinical and Experimental Hypertension, 2020
Noushin Yazdani, Mark S. Kindy, Saeid Taheri
Among sensory mechanisms related to blood flow regulation, baroreflex, and shear stress sensing mechanisms have been extensively studied and found to play critical roles in CBF autoregulation (166,167). The most important baroreceptors are located in the carotid sinus, as well as in the aortic arch. It has been shown that baroreceptor neurons have mechanosensitive ion channels, where they sense arterial blood pressure (168). The mechanism that involves baroreflex sensors to regulate blood pressure changes is named the baroreflex mechanism (BRM). BRM prevents wide fluctuations in arterial blood pressure by controlling the heart rate, vessel contractility, and peripheral resistance. The BRM is mostly recognized for its role in the long term MAP regulation (123). Although BRM similar to the other CBF autoregulation mechanisms, controls blood flow, there are reports that during hypertension BRM influences CBF autoregulation mechanisms (128,166).
NiONPs-induced alteration in calcium signaling and mitochondrial function in pulmonary artery endothelial cells involves oxidative stress and TRPV4 channels disruption
Published in Nanotoxicology, 2022
Ophélie Germande, Magalie Baudrimont, Fabien Beaufils, Véronique Freund-Michel, Thomas Ducret, Jean-François Quignard, Marie-Hélène Errera, Sabrina Lacomme, Etienne Gontier, Stéphane Mornet, Megi Bejko, Bernard Muller, Roger Marthan, Christelle Guibert, Juliette Deweirdt, Isabelle Baudrimont
Other in vitro studies have demonstrated that NiONPs cause oxidative stress and calcium signaling alterations. Both are critical events involved in the physiopathology of cardiovascular diseases such as pulmonary hypertension (PH) (Guibert, Marthan, and Savineau 2007; Lai, Lu, and Wang 2015). Oxidative stress has been identified as the common mechanism of cellular damage after exposure to NPs (Deweirdt et al. 2020). The number of reactive oxygen species (ROS) generated was higher than exposure to larger particles, likely due to NPs higher surface area (Sioutas, Delfino, and Singh 2005). As regards calcium signaling alterations, previous studies have shown that intrapulmonary arteries exposure to engineered NPs alters vascular reactivity (Courtois et al. 2010; Ying et al. 2013). Calcium homeostasis is controlled by calcium intracellular stores (i.e. endoplasmic reticulum and mitochondria), and calcium influx through membrane channels, such as stretch-activated channels (SAC) (Filippini, D’Amore, and D’Alessio 2019). Therefore, alterations of calcium intracellular stores and/or SAC activity may lead to increased cytoplasmic calcium concentrations. SAC include the mechanosensitive ion channels TRPV (Transient Receptor Potential Vanilloid). TRPV1 and TRPV4 expression are increased in vascular cells, and these channels play a role in pulmonary vessels remodeling, a major PH pathophysiological feature (Ducret et al. 2010; Parpaite et al. 2016). In addition, Goswami et al. have suggested that TRPV4 channels are a potential target for NiNPs and participate in cellular homeostasis alteration by regulating microtubules and actin (Goswami et al. 2010). Interestingly, it has been shown that a 4 h-exposure to NiONPs (1–10 µg/mL) increases intracellular calcium concentration in BEAS-2B pulmonary epithelial cells, through an interaction between NiONPs and calcium channels such as TRPV4 (DI Bucchianico et al. 2018).