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Transient Receptor Potential Channels and Itch
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Mahar Fatima, Jingyi Liu, Bo Duan
The TRP channel family is a superfamily of non- or weakly-selective cation tetrameric channels. Activation of TRP channels can depolarize the membrane potential, which can lead to the opening or closing of voltage-gated channels. Based on sequence similarity, TRP family can be divided into seven different sub-families: TRP ‘Ankyrin’ family (TRPA), TRP ‘Canonical’ family (TRPC), TRP ‘Melastatin’ family (TRPM), TRP ‘Mucolipin’ family (TRPML), TRP ‘NOMPC’ (TRPN), TRP ‘Polycystin’ family (TRPP), and TRP ‘Vanilloid’ family (TRPV) (7). TRP channels were initially discovered in the fruit fly Drosophila melanogaster when a trp mutant showed a ‘transient receptor potential’ unlike an expected sustained waveform on the electroretinogram (8). Twenty years later, the first trp gene was cloned in Drosophila melanogaster in 1989 (9), opening avenues to explore the biologically ubiquitous yet unique TRP superfamily.
Neurons
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
The voltage-dependent Na+ channels belong to a single subfamily Nav1 having various subtypes indicated by numbers after the decimal point. At least nine voltage-gated channels have been identified, designated as Nav1.1 to Nav1.9, with different subtypes, expressed in neurons as well as in cardiac, skeletal, and smooth muscle. At least two non-voltage-gated Na+ channels have been identified.
Changes in Transmembrane Signaling Mechanisms During Aging — Cellular and Molecular Aspects
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
Atsushi Miyamoto, George S. Roth
Ligand-gated channels and voltage-gated channels comprise the two major classes of ion channels in excitable membranes.45–47 Ligand-gated channels are sensitive to specific ligands; examples are nicotinic acetylcholine (nACh) receptors, γ-aminobutyric acid (GABAA) receptors, N-methyl-d-aspartate (NMDA) receptors, (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, Ca2+-activated K+ channels, and nucleotide-gated channels. Voltage-gated channels are sensitive to changes in membrane potential; examples are Na+, K+, and Ca2+ channels. G-protein-gated ion channels48,49 are sensitive to specific signal-transducing, membrane-associated G-proteins that act directly on ion channels, making them more likely to open. Direct G-protein gating has already been identified for K+ channels48 and for Ca2+ channels.49
Advances in genetic testing and optimization of clinical management in children and adults with epilepsy
Published in Expert Review of Neurotherapeutics, 2020
Marcello Scala, Amedeo Bianchi, Francesca Bisulli, Antonietta Coppola, Maurizio Elia, Marina Trivisano, Dario Pruna, Tommaso Pippucci, Laura Canafoglia, Simona Lattanzi, Silvana Franceschetti, Carlo Nobile, Antonio Gambardella, Roberto Michelucci, Federico Zara, Pasquale Striano
In the last two decades, significant advances have been accomplished in molecular genetics. The discovery of new causative genes for several epileptic disorders has remarkably improved the knowledge on the epileptogenesis. In particular, the identification of the genes encoding the subunits of voltage-gated channels (sodium, potassium, and chloride channels) and the subunits of the acetylcholine and GABA receptors have provided fundamental insights into the pathogenic mechanisms underlying several epileptic disorders. Accordingly, the development of new drugs specifically targeting mutated proteins and selectively addressing pathogenic mechanisms has opened new scenarios for personalized therapeutic approaches (precision medicine). As an example, the understanding of the pathophysiology of KCNT1-relatd epilepsies has supported the use of quinidine in these conditions [159]. Vipocentine, an alkaloid potentiating GABA-evoked currents, has been successfully used to treat Lennox-Gastaut syndrome caused by GABRB3 mutation [160]. The new compounds MPX-004 and MPX-007 have been developed to selectively block the NMDA receptors containing the NR2A subunit in patients with gain-of-function mutations in GRIN2A [151]. These improvements have also contributed to enhancing the pharmacogenomics, which represents a valuable tool for clinicians to predict the efficacy and tolerability of a specific drug in the single patient.
Effects of extremely low-frequency electromagnetic fields on B16F10 cancer cells
Published in Electromagnetic Biology and Medicine, 2019
Jing-Yau Tang, Te-Wei Yeh, Yu-Ting Huang, Min-Haw Wang, Ling-Sheng Jang
According to previous studies, the effects of EMFs are associated with cell metabolism and ion voltage-gated channel effects. Several studies have proposed that non-specific processes, such as changes in mitochondrial activity, the formation of free radicals, and the promotion of DNA damage, are involved in EMF effects (Roderick and Cook, 2008; Simko et al., 1998; Tsai et al., 2009). Furthermore, research has shown that the mechanisms of EMF effects are related to the ion voltage-gated channels on the cell membrane (Berg, 1999; Destefanis et al., 2015; Lyle et al., 1991; Prevarskaya et al., 2014). These studies consider that EMF exposure can promote ion influx through voltage-gated channels. EMF exposure can increase the concentration of some important ions, such as Ca2+, in the cytosolic, which then changes the metabolic rate of biological functions. Although EMFs have been found to generally affect biological functions, they have also been shown to generate different effects on specific cells and tissues, especially in ELF ranges (Tiwari, 2015).
Juglone as antihypertensive agent acts through multiple vascular mechanisms
Published in Clinical and Experimental Hypertension, 2020
Taseer Ahmad, Taous Khan, Abdul Jabbar Shah
These findings on the vascular reactivity of juglone did not identify a dominating mechanism related to the vascular smooth muscles. Therefore, further insight into other vascular aspects was investigated. Vascular K+ channel activation is known to play an important role in the regulation of vascular tone. There exist different types of K+ channels in the vascular smooth muscles. These include calcium-activated K+ channels (KCa), K+ voltage-gated channels (Kv) and inward rectifying K+ channels (Kir). To see if these K+ channels have played a role in the vasorelaxant effect of juglone, aortic rings were precontracted with phenylephrine and effect was reproduced in the presence of different K+ channel blockers. TEA, blocker of KCa channels (20) was without effect on the vasorelaxant effect of juglone, however, BaCl2, a blocker of Kir channels (61) and 4-aminopyridine, blocker of Kv channels (62) significantly inhibited relaxation to juglone. These exciting findings on juglone indicate that predominate endothelium-independent vasorelaxant mechanism is the activation or opening of Kv and Kir channels. Moreover, past work on BaCl2 has revealed that lower concentrations have shown similar effects. For example, Tyml et al. (63) used 1 µM in capillaries of frog, Ellis et al. (64) used 30 µM in mouse isolated aorta and small mesenteric artery, while others (41,65,66) used 1 mM to block potassium channels (Kir) in rat aorta. So, in comparison with frog capillaries and mouse aorta and small mesenteric artery, we used 1 mM for rat aorta, which is a larger blood vessel in diameter.