{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T18:59:13Z","timestamp":1758049153028,"version":"3.44.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2020,7]]},"DOI":"10.1016\/j.bcp.2020.113961","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T19:43:36Z","timestamp":1586202216000},"page":"113961","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["Voltage-induced structural modifications on M2 muscarinic receptor and their functional implications when interacting with the superagonist iperoxo"],"prefix":"10.1016","volume":"177","author":[{"given":"Ana Laura","family":"L\u00f3pez-Serrano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 J.","family":"De Jes\u00fas-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Zamora-C\u00e1rdenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldo A.","family":"Rodr\u00edguez-Menchaca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Tristani-Firouzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eloy G.","family":"Moreno-Galindo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo A.","family":"Navarro-Polanco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.bcp.2020.113961_b0005","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1074\/jbc.M407783200","article-title":"Mahaut-Smith Direct voltage control of signaling via P2Y1 and other Galphaq-coupled receptors","volume":"280","author":"Martinez-Pinna","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2020.113961_b0010","doi-asserted-by":"crossref","first-page":"24204","DOI":"10.1074\/jbc.M513447200","article-title":"Parnas The metabotropic glutamate G-protein-coupled receptors mGluR3 and mGluR1a are voltage-sensitive","volume":"281","author":"Ohana","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2020.113961_b0015","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1073\/pnas.1212656110","article-title":"Bunemann Voltage regulates adrenergic receptor function","volume":"110","author":"Rinne","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.bcp.2020.113961_b0020","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aac7419","article-title":"Bunemann The mode of agonist binding to a G protein-coupled receptor switches the effect that voltage changes have on signaling","volume":"8","author":"Rinne","year":"2015","journal-title":"Sci. Signal"},{"key":"10.1016\/j.bcp.2020.113961_b0025","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/syn.20509","article-title":"Arhem Voltage-dependence of the human dopamine D2 receptor","volume":"62","author":"Sahlholm","year":"2008","journal-title":"Synapse"},{"key":"10.1016\/j.bcp.2020.113961_b0030","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1016\/j.bbamem.2012.07.027","article-title":"Arhem Voltage sensitivities and deactivation kinetics of histamine H(3) and H(4) receptors","volume":"1818","author":"Sahlholm","year":"2012","journal-title":"BBA"},{"key":"10.1016\/j.bcp.2020.113961_b0035","doi-asserted-by":"crossref","first-page":"e74354","DOI":"10.1371\/journal.pone.0074354","article-title":"Parnas Voltage affects the dissociation rate constant of the m2 muscarinic receptor","volume":"8","author":"Ben","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.bcp.2020.113961_b0040","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature05259","article-title":"Parnas Movement of 'gating charge' is coupled to ligand binding in a G-protein-coupled receptor","volume":"444","author":"Ben-Chaim","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2020.113961_b0045","doi-asserted-by":"crossref","first-page":"22482","DOI":"10.1074\/jbc.M301146200","article-title":"Parnas The M2 muscarinic G-protein-coupled receptor is voltage-sensitive","volume":"278","author":"Ben-Chaim","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2020.113961_b0050","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1073\/pnas.1119424109","article-title":"Bezanilla Depolarization induces a conformational change in the binding site region of the M2 muscarinic receptor","volume":"109","author":"Dekel","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.bcp.2020.113961_b0055","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1007\/s00424-016-1812-y","article-title":"Navarro-Polanco The agonist-specific voltage dependence of M2 muscarinic receptors modulates the deactivation of the acetylcholine-gated K(+) current (I KACh)","volume":"468","author":"Moreno-Galindo","year":"2016","journal-title":"Pflugers Arch."},{"key":"10.1016\/j.bcp.2020.113961_b0060","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.1113\/jphysiol.2013.255166","article-title":"Moreno-Galindo Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes","volume":"591","author":"Navarro-Polanco","year":"2013","journal-title":"J. Physiol."},{"key":"10.1016\/j.bcp.2020.113961_b0065","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1113\/jphysiol.2010.204107","article-title":"Tristani-Firouzi Conformational changes in the M2 muscarinic receptor induced by membrane voltage and agonist binding","volume":"589","author":"Navarro-Polanco","year":"2011","journal-title":"J. Physiol."},{"key":"10.1016\/j.bcp.2020.113961_b0070","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1007\/s00424-018-2196-y","article-title":"Moreno-Galindo The voltage-sensitive cardiac M2 muscarinic receptor modulates the inward rectification of the G protein-coupled, ACh-gated K(+) current","volume":"470","author":"Salazar-Fajardo","year":"2018","journal-title":"Pflugers Arch."},{"key":"10.1016\/j.bcp.2020.113961_b0075","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.mce.2010.07.009","article-title":"When simple agonism is not enough: emerging modalities of GPCR ligands","volume":"331","author":"Smith","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.bcp.2020.113961_b0080","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/S0968-0896(99)00107-8","article-title":"Impicciatore Synthesis and functional characterization of novel derivatives related to oxotremorine and oxotremorine-M","volume":"7","author":"Dallanoce","year":"1999","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bcp.2020.113961_b0085","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/bph.12003","article-title":"Agonists with supraphysiological efficacy at the muscarinic M2 ACh receptor","volume":"169","author":"Schrage","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.bcp.2020.113961_b0090","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1021\/acs.jctc.9b00118","article-title":"Chasing the Full Free Energy Landscape of Neuroreceptor\/Ligand Unbinding by Metadynamics Simulations","volume":"15","author":"Capelli","year":"2019","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bcp.2020.113961_b0095","doi-asserted-by":"crossref","first-page":"12162","DOI":"10.1073\/pnas.1614538113","article-title":"Graded activation and free energy landscapes of a muscarinic G-protein-coupled receptor","volume":"113","author":"Miao","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.bcp.2020.113961_b0100","doi-asserted-by":"crossref","unstructured":"R. Schrage, J. Holze, J. Klockner, A. Balkow, A.S. Klause, A.L. Schmitz, M. De Amici, E. Kostenis, C. Trankle, U. Holzgrabe, K. Mohr New insight into active muscarinic receptors with the novel radioagonist [(3)H]iperoxo. Biochem Pharmacol, 90 (2014), pp. 307\u201319.","DOI":"10.1016\/j.bcp.2014.05.012"},{"key":"10.1016\/j.bcp.2020.113961_b0105","doi-asserted-by":"crossref","unstructured":"A.C. Kruse, A.M. Ring, A. Manglik, J. Hu, K. Hu, K. Eitel, H. Hubner, E. Pardon, C. Valant, P.M. Sexton, A. Christopoulos, C.C. Felder, P. Gmeiner, J. Steyaert, W.I. Weis, K.C. Garcia, J. Wess, B.K. Kobilka Activation and allosteric modulation of a muscarinic acetylcholine receptor Nature, 504 (2013), pp. 101\u20136.","DOI":"10.1038\/nature12735"},{"key":"10.1016\/j.bcp.2020.113961_b0110","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/j.bpj.2016.08.035","article-title":"Ben-Chaim A Novel Voltage Sensor in the Orthosteric Binding Site of the M2 Muscarinic Receptor","volume":"111","author":"Barchad-Avitzur","year":"2016","journal-title":"Biophys. J."},{"key":"10.1016\/j.bcp.2020.113961_b0115","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1113\/jphysiol.2010.204115","article-title":"Navarro-Polanco Relaxation gating of the acetylcholine-activated inward rectifier K+ current is mediated by intrinsic voltage sensitivity of the muscarinic receptor","volume":"589","author":"Moreno-Galindo","year":"2011","journal-title":"J. Physiol."},{"issue":"7","key":"10.1016\/j.bcp.2020.113961_b9000","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1113\/JP273225","article-title":"Molecular mechanisms of Slo2 K+ channel closure","volume":"595","author":"Giese","year":"2017","journal-title":"J. Physiol."},{"key":"10.1016\/j.bcp.2020.113961_b0120","doi-asserted-by":"crossref","unstructured":"B.R. Brooks, C.L. Brooks, 3rd, A.D. Mackerell, Jr., L. Nilsson, R.J. Petrella, B. Roux, Y. Won, G. Archontis, C. Bartels, S. Boresch, A. Caflisch, L. Caves, Q. Cui, A.R. Dinner, M. Feig, S. Fischer, J. Gao, M. Hodoscek, W. Im, K. Kuczera, T. Lazaridis, J. Ma, V. Ovchinnikov, E. Paci, R.W. Pastor, C.B. Post, J.Z. Pu, M. Schaefer, B. Tidor, R.M. Venable, H.L. Woodcock, X. Wu, W. Yang, D.M. York, M. Karplus CHARMM: the biomolecular simulation program. J Comput Chem, 30 (2009), pp. 1545\u2013614.","DOI":"10.1002\/jcc.21287"},{"key":"10.1016\/j.bcp.2020.113961_b0125","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"Im CHARMM-GUI: a web-based graphical user interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.bcp.2020.113961_b0130","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1021\/acs.jctc.5b00935","article-title":"Im CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM\/OpenMM Simulations Using the CHARMM36 Additive Force Field","volume":"12","author":"Lee","year":"2016","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bcp.2020.113961_b0135","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0010-4655(95)00042-E","article-title":"Drunen GROMACS: A message-passing parallel molecular dynamics implementation","volume":"91","author":"Berendsen","year":"1995","journal-title":"Comput. Phys. Commun."},{"key":"10.1016\/j.bcp.2020.113961_b0140","doi-asserted-by":"crossref","first-page":"7830","DOI":"10.1021\/jp101759q","article-title":"Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types","volume":"114","author":"Klauda","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.bcp.2020.113961_b0145","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1002\/jcc.24829","article-title":"Im CHARMM-GUI ligand reader and modeler for CHARMM force field generation of small molecules","volume":"38","author":"Kim","year":"2017","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.bcp.2020.113961_b0150","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N -log(N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J Chern Phys."},{"key":"10.1016\/j.bcp.2020.113961_b0155","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single crystals: A new molecular dynamics method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys."},{"key":"10.1016\/j.bcp.2020.113961_b0160","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1073\/pnas.1800756115","article-title":"McCammon Mechanism of the G-protein mimetic nanobody binding to a muscarinic G-protein-coupled receptor","volume":"115","author":"Miao","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.bcp.2020.113961_b0165","doi-asserted-by":"crossref","first-page":"6239","DOI":"10.1073\/pnas.1037595100","article-title":"Agonist unbinding from receptor dictates the nature of deactivation kinetics of G protein-gated K+ channels","volume":"100","author":"Benians","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.bcp.2020.113961_b0170","doi-asserted-by":"crossref","first-page":"47512","DOI":"10.1074\/jbc.M108652200","article-title":"Hein Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents","volume":"276","author":"Bunemann","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2020.113961_b0175","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1124\/mol.116.104950","article-title":"Navarro-polanco pharmacological conversion of a cardiac inward rectifier into an outward rectifier potassium channel","volume":"90","author":"Moreno-Galindo","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.bcp.2020.113961_b0180","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1074\/jbc.M205325200","article-title":"Bunemann Regulation of the inward rectifying properties of G-protein-activated inwardly rectifying K+ (GIRK) channels by Gbeta gamma subunits","volume":"278","author":"Hommers","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2020.113961_b0185","unstructured":"Y. Kurachi, Muscarinic acetylcholine-gated K+ channels in mammalian heart., in: Reuss L, Russell JM, S. G (Eds.), Regulation of Potassium Transport Across Biological Membranes, The University of Texas Press, Autin, TX, 1990, pp. 403-428."},{"key":"10.1016\/j.bcp.2020.113961_b0190","first-page":"H681","article-title":"Acetylcholine activation of K+ channels in cell-free membrane of atrial cells","volume":"251","author":"Kurachi","year":"1986","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.bcp.2020.113961_b0195","doi-asserted-by":"crossref","unstructured":"P.J. Pfaffinger, J.M. Martin, D.D. Hunter, N.M. Nathanson, B. Hille GTP-binding proteins couple cardiac muscarinic receptors to a K channel Nature, 317 (1985), pp. 536-8.","DOI":"10.1038\/317536a0"},{"key":"10.1016\/j.bcp.2020.113961_b0200","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.neuropharm.2011.06.022","article-title":"Arhem Agonist-specific voltage sensitivity at the dopamine D2S receptor\u2013molecular determinants and relevance to therapeutic ligands","volume":"61","author":"Sahlholm","year":"2011","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.bcp.2020.113961_b0205","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.bbrc.2008.07.052","article-title":"Arhem Differential voltage-sensitivity of D2-like dopamine receptors","volume":"374","author":"Sahlholm","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.bcp.2020.113961_b0210","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nature18324","article-title":"Allosteric coupling from G protein to the agonist-binding pocket in GPCRs","volume":"535","author":"DeVree","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2020.113961_b0215","doi-asserted-by":"crossref","first-page":"7459","DOI":"10.1074\/jbc.M109.094011","article-title":"Identification of orthosteric and allosteric site mutations in M2 muscarinic acetylcholine receptors that contribute to ligand-selective signaling bias","volume":"285","author":"Gregory","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2020.113961_b0220","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature10753","article-title":"Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist","volume":"482","author":"Haga","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2020.113961_b0225","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1038\/s41467-019-11062-7","article-title":"Dror Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs","volume":"10","author":"Hollingsworth","year":"2019","journal-title":"Nat. Commun."}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295220301891?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295220301891?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T13:15:07Z","timestamp":1757769307000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295220301891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":46,"alternative-id":["S0006295220301891"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2020.113961","relation":{},"ISSN":["0006-2952"],"issn-type":[{"type":"print","value":"0006-2952"}],"subject":[],"published":{"date-parts":[[2020,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Voltage-induced structural modifications on M2 muscarinic receptor and their functional implications when interacting with the superagonist iperoxo","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2020.113961","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"113961"}}