P2X receptors are calcium permeable ligand-gated ion channels activated by ATP. Their role as cell surface receptors for extracellular ATP released physiologically by mammalian cells is well established. However, the cellular function of P2X receptor subtypes that populate the membranes of intracellular compartments is not defined. An initial report described how intracellular P2X receptors control the function of the contractile vacuole, an osmoregulatory organelle in Dictyostelium and other protists, and that genetic disruption of P2X receptors severely impaired cell volume control during hypotonic stress. However, later studies refuted a functional role of intracellular P2X receptors in Dictyostelium. Here we provide evidence that the discrepancies reported between the studies are due to the laboratory strain of Dictyostelium employed, which display different phenotypes in response to hypotonic stress and a varied dependency upon P2X receptors for osmoregulation. We use the recent discovery that intracellular P2X receptors are novel calcium release channels to provide some mechanistic insight in an effort to explain why the strain variance may exist.
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http://dx.doi.org/10.4161/chan.22737 | DOI Listing |
J Physiol Sci
January 2025
Department of Basic Veterinary Science, Laboratory of Physiology, Joint Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, 501-1193, Gifu, Japan; Department of Basic Veterinary Science, Laboratory of Physiology, Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, 501-1193, Gifu, Japan; Division of Animal Medical Science, Center for One Medicine Innovative Translational Research (COMIT), Gifu University Institute for Advanced Study, 1-1 Yanagido, 501-1193, Gifu, Japan.
Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer.
View Article and Find Full Text PDFLife Sci
January 2025
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:
The pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in over 7 million global fatalities and billions of individuals diagnosed with COVID-19. Acute and chronic muscle impairment associated with SARS-CoV-2 infection affected a substantial number of patients, leading to the development of symptoms such as fatigue, muscle pain, and exercise intolerance. Our study introduces an animal model to improve understanding of the pathogenicity caused by SARS-CoV-2 in human skeletal muscle.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR 97239, USA.
P2X receptors (P2XRs) are adenosine 5'-triphosphate (ATP)-gated ion channels comprising homomeric and heteromeric trimers of seven subtypes (P2X1-P2X7) that confer different rates of desensitization. The helical recoil model of P2XR desensitization proposes stability of the cytoplasmic cap sets the rate of desensitization, but timing of its formation is unclear for slow-desensitizing P2XRs. We report cryo-electron microscopy structures of full-length wild-type human P2X4 receptor in apo closed, antagonist-bound inhibited, and ATP-bound desensitized states.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
January 2025
Pharmaceutical Institute, Pharmacology and Toxicology, University of Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, Germany.
Lipopolysaccharide (LPS)-neutralizing peptides are emerging as new potential therapeutic modalities to treat sepsis and skin infections. Purinergic ligand-gated ion channels (P2X receptors) play a critical role in various biological processes, including inflammation. Recent drug development efforts have significantly focused on the modulation of P2X receptors.
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2024
Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo 1781421, Chile.
P2X receptor channels are widely expressed in the CNS, where they have multiple functions in health and disease. The rat P2X2a (rP2X2a) receptor channel is modulated by copper, an essential trace element that plays important roles in synaptic modulation and neurodegenerative disorders. Although essential extracellular amino acids that coordinate copper have been identified, the exact mechanism of copper-induced modulation has not been yet elucidated.
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