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Introduction To Receptors
Published in John C. Matthews, Fundamentals of Receptor, Enzyme, and Transport Kinetics, 2017
When this receptor-modulated cation channel opens, sodium and calcium ions flow into the muscle cell from the outside, moving down their electrochemical gradients. This flow of positive charges into the cell reduces the inside negative electrical potential compared with the outside of the cell. This localized “depolarization” of the membrane is sensed by nearby voltage sensitive sodium channels. The voltage sensitive sodium channels respond by opening to produce a spreading depolarization of the muscle cell membrane.
The Calcium-Calmodulin System
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Calcium ions play an important role in the regulation of cellular activity and metabolism, and calcium is considered, in conjunction with cyclic nucleotides, as a second messenger to extracellular signaling agents such as hormones, growth factors, regulatory peptides, and neurotransmitters.40 An increase in the [Ca2+]i may be caused by Ca2+ entry into the cells via ion channels in the plasma membrane or by Ca2+ release from intracellular stores. Ca2+ entry into the cell may occur by four major types of mechanisms: (1) a receptor-mediated channel coupled to intracellular second messengers; (2) a Ca2+ leak channel dependent on the Ca2+ electrochemical gradient; (3) a stretch-activated nonselective cation channel; and (4) internal Na+-dependent Ca2+ entry (Na+/Ca2+ exchange).41 Both Ca2+ entry and intracellular Ca2+ mobilization can be observed in stimulated cells. Treatment of Ehrlich ascites tumor cells with micromolar concentrations of ATP induces a rapid and transient increase in [Ca2+]i by mobilizing an intracellular, nonmitochondrial pool of [Ca2+]i and increasing Ca2+ permeability at the level of the plasma membrane.42 Other nucleotide triphosphates, including GTP, induce Ca2+ transient increases that are identical to those produced by ATP.
Nerve-to-Muscle Signals
Published in Peter W. Hochachka, Muscles as Molecular and Metabolic Machines, 2019
In preparations from both species (Figure 2–3), the end-plate channel occurs as a 250 kDa oligomeric protein, formed from four different kinds of subunits with molecular masses of 40, 50, 60, and 65 kDa (Wan and Lindstrom, 1984). The peptides α, β, γ, and δ exist in a pentameric stoichiometry, α2βγδ in the original complex, making a total molecular mass of 268 kDa. In addition, about 75 carbohydrate residues (galactose, mannose, glucose, and N-acetylglucosamine) are attached as oligosaccharide chains, some to each peptide subunit, and the protein has several sites of phosphorylation. As in all other membrane proteins, glycosylation probably defines regions of protein facing the extracellular medium. The majority of the receptor is exposed on the extracellular surface and four or five transmembranous-helical domains are thought to exist in each subunit. The cation channel seems to traverse the membrane through the center of the receptor, and the subunits are apparently oriented around this central channel. Each subunit donates a domain to form the channel, as might the staves of a barrel. Viewed from the top by electron microscopy, the receptor looks like a doughnut; viewed from the side, it looks somewhat like a funnel (Wan and Lindstrom, 1984). Experiments with antibodies and water-soluble covalent modifiers show that each subunit also displays a cytosolic domain exposed to the intracellular medium. Hence α, β, γ, and δ each extends fully across the membrane. The intact, purified AChR complex includes all the major functions of the ionic channel since, when it is incorporated into lipid bilayers, it assembles into channels that express appropriate ionic selectivity, conductance, and responses to agonists and antagonists (Tank et al., 1983).
Morphological study of the postnatal hippocampal development in the TRPV1 knockout mice
Published in Temperature, 2023
Melinda Boros, Noémi Sóki, Abigél Molnár, Hajnalka Ábrahám
Transient receptor potential vanilloid 1 (TRPV1) is one of the most studied members of vanilloid subfamily of transient receptor potential (TRP) ion channels. TRPV1 can be activated by capsaicin and other exogenous (e.g. resiniferatoxin) and endogenous (e.g. endocannabinoids) ligands, low pH, high temperature, or by mechanical effects [1-5]. The possibility of the existence and the first hypothetical model of a capsaicin receptor were proposed in the 1970s by Aranka Jancsó-Gábor and János Szolcsányi [6,7]. Later its existence as a capsaicin-gated cation channel was identified by 8. TRPV1 was first cloned by 9, from rat sensory ganglia. Being a non-selective, chemo- and heat-sensitive cation channel, TRPV1 has polymodal sensory function. It plays a key role in integration of inflammatory and nociceptive stimuli; therefore, TRPV1 became a potent target in pharmacological researches [10–21].
Participation of signaling proteins in sperm hyperactivation
Published in Systems Biology in Reproductive Medicine, 2022
Joaquín Cordero-Martínez, Guadalupe Elizabeth Jimenez-Gutierrez, Charmina Aguirre-Alvarado, Verónica Alacántara-Farfán, Germán Chamorro-Cevallos, Ana L. Roa-Espitia, Enrique O. Hernández-González, Lorena Rodríguez-Páez
CatSper in one of the wide variety of channels located in the sperm flagellum. It is a calcium channel specifically expressed in spermatozoa and is essential for sperm functions and fertility (Mannowetz et al. 2017; Brenker et al. 2018). This channel is responsible for the increase in [Ca2+]i, which is required for capacitation and hyperactivation (Marquez and Suarez 2004; Tamburrino et al. 2014; Diao et al. 2017). The CatSper family comprises of four members (CatSper 1-4), all of which is required for hyperactivation (Qi et al. 2007). Recently, new auxiliary subunits present in the CatSper structure have been identified. They combine to form an ultracomplex (CATSPERβ, γ, δ, ε, ζ, and EFCAB9) (Lin et al. 2021), being the α-chain the one that selectively permits the entry of Ca2+ (Navarro et al. 2008; Sun et al. 2017). CatSper from human spermatozoa is activated by the human follicular fluid and progesterone (Strünker et al. 2011; Brown et al. 2017; Zou et al. 2017). It is sensitive to alkalinization of pHi and is a voltage-gated channel (Torrezan-Nitao et al. 2021). Owing to its important functions, this cation channel is considered to be the main target for future male contraceptive methodologies. CatSper1 null mice (Catsper−/−) failed to facilitate hyperactivation and fertilize an intact oocyte; additionally, the influx of Ca2+ induced by cAMP signaling was abolished (Ren et al. 2001).
Subanesthetic ketamine: the way forward for pain management in sickle cell disease patients?
Published in Expert Review of Hematology, 2022
Raissa Nobrega, Veronica Carullo, Swee Lay Thein, Zenaide M.N. Quezado
A dissociative anesthetic, ketamine has been used since the 1960s and proven safe and effective in many clinical settings including battlefield rescues, emergency departments, and operating rooms [11]. Ketamine’s principal mechanism of action is the noncompetitive blockade of the NMDA receptor, a cation channel mostly located in excitatory synapses (Figure 1). However, ketamine also affects opioidergic, GABAergic, monoaminergic, and muscarinic neurotransmissions, as well as substance P, alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA), and sigma receptors signaling [11]. The understanding that activation of NMDA receptors has been implicated in the development of central sensitization, inflammatory, nociceptive, and neuropathic pain, as well as of opioid tolerance and opioid-induced hyperalgesia provides the rationale for the use of subanesthetic ketamine for the treatment of acute and chronic pain [12–14].