{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T22:55:50Z","timestamp":1761519350954,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biology, University of Kentucky."},{"name":"Personal funds (R.L.C.)."},{"name":"Chellgren Endowed Funding (R.L.C.)."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bacterial septicemia is commonly induced by Gram-negative bacteria. The immune response is triggered in part by the secretion of bacterial endotoxin lipopolysaccharide (LPS). LPS induces the subsequent release of inflammatory cytokines which can result in pathological conditions. There is no known blocker to the receptors of LPS. The Drosophila larval muscle is an amendable model to rapidly screen various compounds that affect membrane potential and synaptic transmission such as LPS. LPS induces a rapid hyperpolarization in the body wall muscles and depolarization of motor neurons. These actions are blocked by the compound doxapram (10 mM), which is known to inhibit a subtype of the two-P-domain K+ channel (K2P channels). However, the K2P channel blocker PK-THPP had no effect on the Drosophila larval muscle at 1 and 10 mM. These channels are activated by chloroform, which also induces a rapid hyperpolarization of these muscles, but the channels are not blocked by doxapram. Likewise, chloroform does not block the depolarization induced by doxapram. LPS blocks the postsynaptic glutamate receptors on Drosophila muscle. Pre-exposure to doxapram reduces the LPS block of these ionotropic glutamate receptors. Given that the larval Drosophila body wall muscles are depolarized by doxapram and hyperpolarized by chloroform, they offer a model to begin pharmacological profiling of the K2P subtype channels with the potential of identifying blockers for the receptors to mitigate the actions of the Gram-negative endotoxin LPS.<\/jats:p>","DOI":"10.3390\/ijms232415787","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T01:56:06Z","timestamp":1670896566000},"page":"15787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hyperpolarization Induced by Lipopolysaccharides but Not by Chloroform Is Inhibited by Doxapram, an Inhibitor of Two-P-Domain K+ Channel (K2P)"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7234-4361","authenticated-orcid":false,"given":"Robin L.","family":"Cooper","sequence":"first","affiliation":[{"name":"Department of Biology, University of Kentucky, Lexington, KY 40506-0225, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7166-0776","authenticated-orcid":false,"given":"Rebecca M.","family":"Krall","sequence":"additional","affiliation":[{"name":"Department of STEM Education, University of Kentucky, Lexington, KY 40506-0001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1126\/science.145.3634.783","article-title":"Lipopolysaccharide of the gram-negative cell wall","volume":"145","author":"Osborn","year":"1964","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1111\/j.1574-6976.2010.00231.x","article-title":"RTX proteins: A highly diverse family secreted by a common mechanism","volume":"34","author":"Bumba","year":"2010","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21129","DOI":"10.1074\/jbc.M009164200","article-title":"Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. transfer from CD14 to TLR4 and MD-2","volume":"276","author":"Soldau","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1017\/S031716710005335X","article-title":"Progress in clinical neurosciences: Sepsis-associated encephalopathy: Evolving concepts","volume":"30","author":"Wilson","year":"2003","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/physrev.00028.2014","article-title":"The sick and the weak: Neuropathies\/myopathies in the critically ill","volume":"95","author":"Friedrich","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"433","DOI":"10.4149\/gpb_2018001","article-title":"Exercise preconditioning attenuates atrophic mediators and preserves muscle mass in acute sepsis","volume":"37","author":"Fujino","year":"2018","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1001\/jama.1996.03530300054040","article-title":"The spectrum of septic encephalopathy definitions, etiologies, and mortalities","volume":"275","author":"Eidelman","year":"1996","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1093\/molbev\/msx168","article-title":"Rapidly evolving Toll-3\/4 genes encode male-specific Toll-like receptors in Drosophila","volume":"34","author":"Levin","year":"2017","journal-title":"Mol. Biol. Evol."},{"key":"ref_9","first-page":"210","article-title":"Toll-like receptors: An overview from invertebrates to vertebrates","volume":"8","author":"Coscia","year":"2011","journal-title":"Invert. Surv. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.0105-2896.2004.0117.x","article-title":"Invertebrate immune systems\u2014Not homogeneous, not simple, not well understood","volume":"198","author":"Loker","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.dci.2013.05.014","article-title":"The Drosophila IMD pathway in the activation of the humoral immune response","volume":"42","author":"Kleino","year":"2014","journal-title":"Dev. Com. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/nature734","article-title":"The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein","volume":"416","author":"Gottar","year":"2002","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13705","DOI":"10.1073\/pnas.212301199","article-title":"Overexpression of a pattern-recognition receptor, peptidoglycan recognition protein-LE, activates imd\/relish mediated antibacterial defense and the prophenoloxidase cascade in Drosophila larvae","volume":"99","author":"Takehana","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.0105-2896.2004.0130.x","article-title":"The immune response of Drosophila melanogaster","volume":"198","author":"Leclerc","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13772","DOI":"10.1073\/pnas.97.25.13772","article-title":"A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster","volume":"97","author":"Werner","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1534\/genetics.115.180208","article-title":"The transgenic RNAi project at Harvard Medical School: Resources and validation","volume":"201","author":"Perkins","year":"2015","journal-title":"Genetics"},{"key":"ref_17","first-page":"33","article-title":"The effects of bacterial endotoxin (LPS) on cardiac and synaptic function in various animal models: Larval Drosophila, crayfish, crab, and rodent","volume":"16","author":"Anyagaligbo","year":"2020","journal-title":"Internat. J. Zool. Res."},{"doi-asserted-by":"crossref","unstructured":"Vacassenno, R.M., Haddad, C.N., and Cooper, R.L. (2022). Lipopolysaccharide (LPS) action on hyperpolarizing membrane potential: Antagonized by the K2P channel blocker, Doxapram, and independent of calcium activated potassium channels, in review.","key":"ref_18","DOI":"10.1016\/j.cbpc.2023.109571"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1097\/00000542-198601000-00010","article-title":"Do anesthetics fluidize membranes?","volume":"64","author":"Ueda","year":"1986","journal-title":"Anesthesiology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"936","DOI":"10.2174\/1570159X18666200227125854","article-title":"The effects of general anesthetics on synaptic transmission","volume":"18","author":"Hao","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.tips.2005.05.003","article-title":"Structure and function of two-pore-domain K+ channels: Contributions from genetic model organisms","volume":"26","author":"Buckingham","year":"2005","journal-title":"Trends Pharmacol. Sci."},{"doi-asserted-by":"crossref","unstructured":"Zheng, J., and Trudeau, M.C. (2015). Two-Pore Domain Potassium Channels. Handbook of Ion Channels, CRC Press. [1st ed.].","key":"ref_22","DOI":"10.1201\/b18027"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13256","DOI":"10.1073\/pnas.93.23.13256","article-title":"ORK1, a potassium-selective leak channel with two pore domains cloned from Drosophila melanogaster by expression in Saccharomyces cerevisiae","volume":"93","author":"Goldstein","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s109-1998-8100-0","article-title":"Sequence and function of the two P domain potassium channels: Implications of an emerging superfamily","volume":"76","author":"Goldstein","year":"1998","journal-title":"J. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"65","DOI":"10.33594\/000000338","article-title":"Pathophysiological role of K2P channels in human diseases","volume":"55","author":"Lee","year":"2021","journal-title":"Cell Physiol. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ejphar.2014.05.056","article-title":"Inhibition of cardiac two-pore-domain K+ (K2P) channels--an emerging antiarrhythmic concept","volume":"738","author":"Schmidt","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1213\/01.ane.0000194289.34345.63","article-title":"The ventilatory stimulant doxapram inhibits TASK tandem pore (K2P) potassium channel function but does not affect minimum alveolar anesthetic concentration","volume":"102","author":"Cotten","year":"2006","journal-title":"Anesth. Analg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1213\/01.ANE.0000180198.13467.DF","article-title":"Doxapram only slightly reduces the shivering threshold in healthy volunteers","volume":"101","author":"Komatsu","year":"2005","journal-title":"Anesth. Analg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.1527-3458.2006.00236.x","article-title":"A new look at the respiratory stimulant doxapram","volume":"12","author":"Yost","year":"2006","journal-title":"CNS Drug Rev. Fall-Winter"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s11940-012-0201-x","article-title":"Overview of therapeutic hypothermia","volume":"14","author":"Song","year":"2012","journal-title":"Curr. Treat. Options. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e13361","DOI":"10.1111\/apha.13361","article-title":"Effects of the ventilatory stimulant, doxapram on human TASK-3 (KCNK9, K2P9.1) channels and TASK-1 (KCNK3, K2P3.1) channels","volume":"228","author":"Cunningham","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1159\/000448941","article-title":"Doxapram treatment for apnea of prematurity: A systematic review","volume":"111","author":"Vliegenthart","year":"2017","journal-title":"Neonatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/S0140-6736(80)90189-0","article-title":"Interferon in human serum after injection of endotoxin","volume":"316","author":"Sauter","year":"1980","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1126\/science.287.5461.2185","article-title":"The genome sequence of Drosophila melanogaster","volume":"287","author":"Adams","year":"2000","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0896-6273(00)81135-6","article-title":"Ion channels and synaptic organization: Analysis of the Drosophila genome","volume":"26","author":"Littleton","year":"2000","journal-title":"Neuron"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mce.2011.11.009","article-title":"TRESK: The lone ranger of two-pore domain potassium channels","volume":"353","author":"Enyedi","year":"2012","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/164_2021_462","article-title":"The pharmacology of two-pore domain potassium channels","volume":"267","author":"Kamuene","year":"2021","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.1093\/emboj\/16.17.5464","article-title":"TASK, a human background K+ channel to sense external pH variations near physiological pH","volume":"16","author":"Duprat","year":"1997","journal-title":"EMBO J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9340","DOI":"10.1074\/jbc.275.13.9340","article-title":"TASK-3, a new member of the tandem pore K(+) channel family","volume":"275","author":"Kim","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16650","DOI":"10.1074\/jbc.M000030200","article-title":"TASK-3, a novel tandem pore domain acid-sensitive K+ channel. An extracellular histidine as pH sensor","volume":"275","author":"Rajan","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.2174\/1381612054546824","article-title":"Physiology and pharmacology of two-pore domain potassium channels","volume":"11","author":"Kim","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S1535-6108(03)00054-0","article-title":"Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene","volume":"3","author":"Mu","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1385\/JMN:25:1:037","article-title":"A TASK3 channel (KCNK9) mutation in a genetic model of absence epilepsy","volume":"25","author":"Holter","year":"2005","journal-title":"J. Mol. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/8084","article-title":"Inhalational anesthetics activate two-pore-domain background K channels","volume":"2","author":"Patel","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1124\/mol.118.115303","article-title":"A small-molecule compound selectively activates K2P channel TASK-3 by acting at two distant clusters of residues","volume":"96","author":"Tian","year":"2019","journal-title":"Mol. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.cbpb.2005.01.019","article-title":"The physiological and behavioral effects of carbon dioxide on Drosophila melanogaster larvae","volume":"140","author":"Badre","year":"2005","journal-title":"Comp. Biochem. Physiol. A."},{"key":"ref_47","first-page":"109497","article-title":"The effects on resting membrane potential and synaptic transmission by Doxapram (blocker of K2P channels) at the Drosophila neuromuscular junction","volume":"263","author":"Vacassenno","year":"2023","journal-title":"Comp. Biochem. Physiol. C"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00210-019-01751-x","article-title":"Chloroform is a potent activator of cardiac and neuronal Kir3 channels","volume":"393","author":"Kollert","year":"2020","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"20977","DOI":"10.1074\/jbc.M610692200","article-title":"Determinants of the anesthetic sensitivity of two-pore domain acid-sensitive potassium channels: Molecular cloning of an anesthetic-activated potassium channel from Lymnaea stagnalis","volume":"282","author":"Caley","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-981-13-0529-0_1","article-title":"Drosophila as a model organism","volume":"1076","author":"Yamaguchi","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1242\/dmm.023762","article-title":"Drosophila tools and assays for the study of human diseases","volume":"9","author":"Ugur","year":"2016","journal-title":"Dis. Model. Mech."},{"doi-asserted-by":"crossref","unstructured":"Ecovoiu, A.A., Ratiu, A.C., Micheu, M.M., and Chifiriuc, M.C. (2022). Inter-Species Rescue of Mutant Phenotype-The Standard for Genetic Analysis of Human Genetic Disorders in Drosophila melanogaster Model. Int. J. Mol. Sci., 23.","key":"ref_52","DOI":"10.3390\/ijms23052613"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41581-022-00561-4","article-title":"Drosophila melanogaster: A simple genetic model of kidney structure, function and disease","volume":"18","author":"Dow","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"912977","DOI":"10.3389\/fpain.2022.912977","article-title":"Cellular pathogenesis of chemotherapy-induced peripheral neuropathy: Insights from Drosophila and Human-engineered skin models","volume":"3","author":"Shin","year":"2022","journal-title":"Front. Pain Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1146\/annurev.genom.7.080505.115758","article-title":"Of flies and man: Drosophila as a model for human complex traits","volume":"7","author":"Mackay","year":"2006","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e01430","DOI":"10.1016\/j.heliyon.2019.e01430","article-title":"The effects of a bacterial endotoxin LPS on synaptic transmission at the neuromuscular junction","volume":"5","author":"Cooper","year":"2019","journal-title":"Heliyon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e13876","DOI":"10.14814\/phy2.13876","article-title":"A1899, PK-THPP, ML365, and Doxapram inhibit endogenous TASK channels and excite calcium signaling in carotid body type-1 cells","volume":"6","author":"Huskens","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/259489a0","article-title":"Synaptic transmission reversibly conditioned by single-gene mutation in Drosophila melanogaster","volume":"259","author":"Ikeda","year":"1976","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1113\/jphysiol.1983.sp014649","article-title":"Ion currents in Drosophila flight muscles","volume":"337","author":"Salkoff","year":"1983","journal-title":"J. Physiol."},{"doi-asserted-by":"crossref","unstructured":"Potter, R., Meade, A., Potter, S., and Cooper, R.L. (2021). Rapid and direct action of lipopolysaccharides (LPS) on skeletal muscle of larval Drosophila. Biology, 10.","key":"ref_60","DOI":"10.3390\/biology10121235"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/jez.620","article-title":"The effects of acute carbon dioxide on behavior and physiology in Procambarus clarkii","volume":"313A","author":"Bierbower","year":"2010","journal-title":"J. Exp. Zool."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/brb3.106","article-title":"Comparative study of environmental factors influencing motor task learning and memory retention in sighted and blind crayfish","volume":"3","author":"Bierbower","year":"2013","journal-title":"Brain Behav."},{"key":"ref_63","first-page":"15","article-title":"The effects of bacterial endotoxin (LPS) on cardiac function in a medicinal blow fly (Phaenicia sericata) and a fruit fly (Drosophila melanogaster)","volume":"217","author":"Anyagaligbo","year":"2019","journal-title":"Comp. Biochem. Physiol. C"},{"doi-asserted-by":"crossref","unstructured":"Istas, O., Greenhalgh, A., and Cooper, R.L. (2019). The effects of a bacterial endotoxin on behavior and sensory-CNS-motor circuits in Drosophila melanogaster. Insects, 10.","key":"ref_64","DOI":"10.3390\/insects10040115"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3923\/jpt.2020.65.72","article-title":"Repetitive exposure to bacterial endotoxin LPS alters synaptic transmission","volume":"15","author":"Istas","year":"2020","journal-title":"J. Pharmacol. Toxicol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"110557","DOI":"10.1016\/j.cbpa.2019.110557","article-title":"Effects of bacterial endotoxin (LPS) on the cardiac function, neuromuscular transmission and sensory-CNS-motor nerve circuit: A crustacean model","volume":"237","author":"Saelinger","year":"2019","journal-title":"Comp. Biochem. Physiol. A"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1213\/01.ane.0000168447.87557.5a","article-title":"Species-specific differences in response to anesthetics and other modulators by the K2P channel TRESK","volume":"101","author":"Keshavaprasad","year":"2005","journal-title":"Anesth. Analg."},{"doi-asserted-by":"crossref","unstructured":"Park, H., Kim, E.-J., Ryu, J.H., Lee, D.K., Hong, S.-G., Han, J., Han, J., and Kang, D. (2018). Verapamil inhibits TRESK (K2P18.1) current in trigeminal ganglion neurons independently of the blockade of Ca2+ influx. Int. J. Mol. Sci., 19.","key":"ref_68","DOI":"10.3390\/ijms19071961"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1213\/ANE.0b013e318284469d","article-title":"TASK-1 (KCNK3) and TASK-3 (KCNK9) tandem pore potassium channel antagonists stimulate breathing in isoflurane-anesthetized rats","volume":"116","author":"Cotton","year":"2013","journal-title":"Anesth. Analg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"566","DOI":"10.3390\/neurosci3040041","article-title":"The effect of doxapram on proprioceptive neurons: Invertebrate model","volume":"3","author":"Ison","year":"2022","journal-title":"NeuroSci"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/BF00215114","article-title":"Improved stability of Drosophila larval neuromuscular preparation in haemolymph-like physiological solutions","volume":"175","author":"Stewart","year":"1994","journal-title":"J. Comp. Physiol. A"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00359-013-0864-0","article-title":"Analysis of various physiological salines for heart rate, CNS function, and synaptic transmission at neuromuscular junctions in Drosophila melanogaster larvae","volume":"200","author":"Titlow","year":"2014","journal-title":"J. Comp. Physiol. A"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.femsle.2005.05.041","article-title":"Rapid and quantitative detection of blood Serratia marcescens by a real-time PCR assay: Its clinical application and evaluation in a mouse infection model","volume":"248","author":"Iwaya","year":"2005","journal-title":"FEMS Microbiol. 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