Jerod Scott Denton, Ph.D.

Professor

jerod.s.denton@vanderbilt.edu

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Faculty Appointments
Professor of Anesthesiology Professor of Pharmacology
Education
Ph.D., Physiology, Dartmouth College, Hanover, New HampshireM.S., Physiology, University of Central Arkansas, Conway, ArkansasB.S., Biology, University of Central Arkansas, Conway, Arkansas
Office Address
Department of Anesthesiology 1161 21st Ave Room T-4208 MCN
Nashville, TN 37232-2520
Research Description
The Denton Laboratory investigates the fundamental biology and therapeutic potential of ion channels, a diverse class of membrane proteins that control electrical signaling, ion homeostasis, cell volume, secretion, and cellular communication throughout the body. Our mission is to transform discoveries in ion channel physiology into novel medicines and research tools that address major unmet medical needs.

Our research spans the interface of basic science, chemical biology, pharmacology, and drug discovery, leveraging expertise in high-throughput screening, electrophysiology, medicinal chemistry, molecular modeling, structural biology, and translational physiology. By integrating these approaches, we seek to understand how ion channels function in health and disease while developing first-in-class small molecules that can serve as pharmacological probes and future therapeutic leads.

A major focus of the laboratory is the inward rectifier potassium (Kir) channel family, which regulates essential physiological processes in the kidney, cardiovascular system, nervous system, endocrine organs, and epithelia. Human genetics and animal studies have implicated Kir channels in hypertension, arrhythmias, kidney disease, pain, and other disorders, yet many family members have historically lacked selective pharmacological tools. The Denton Laboratory has been a leader in developing the molecular pharmacology of these channels, creating novel chemical probes that are revealing their physiological functions and therapeutic potential.

One of our most active translational programs focuses on renal potassium channels as novel targets for hypertension and cardiovascular disease. We have pioneered the development of inhibitors and probes for kidney-expressed channels including Kir1.1 (ROMK), Kir4.1/Kir5.1, and Kir7.1. These efforts are motivated by compelling human genetic evidence suggesting that selective modulation of renal ion transport pathways may lower blood pressure through mechanisms distinct from currently available diuretics. Our goal is to develop next-generation therapeutics that provide effective blood pressure control while minimizing adverse effects.

Beyond Kir channels, our laboratory studies emerging ion channel targets with broad relevance to human disease. We have ongoing programs focused on LRRC8 volume-regulated anion channels (VRACs), which play key roles in cell-volume regulation, inflammation, cancer biology, and intercellular signaling. By developing selective modulators and molecular probes for LRRC8 channel complexes, we seek to uncover previously inaccessible aspects of anion channel physiology and evaluate their therapeutic potential across multiple disease settings.

We are also advancing the pharmacology of TMEM175, an unusual lysosomal potassium channel that has emerged as an important genetic risk factor for Parkinson's disease and other neurodegenerative disorders. TMEM175 regulates lysosomal function, a process central to cellular quality control and neuronal health. Through innovative assay development and screening technologies, our laboratory has identified novel TMEM175 modulators that are enabling mechanistic studies and laying the groundwork for future therapeutic strategies targeting neurodegeneration.

Another exciting area of research in the laboratory is the development of non-hormonal contraceptives. In collaboration with investigators in reproductive biology, medicinal chemistry, and translational pharmacology, we have helped establish the sperm-specific potassium channel SLO3 as a promising contraceptive target. Our work led to the discovery of the first selective SLO3 inhibitors and demonstrated that pharmacological inhibition of this channel disrupts critical sperm functions required for fertilization. These studies support the development of a completely new class of reversible, non-hormonal contraceptives and highlight the power of ion channel pharmacology to address important challenges in reproductive health.

The Denton Laboratory provides a highly collaborative and interdisciplinary training environment where students and postdoctoral fellows participate in all phases of the scientific discovery process, from target identification and assay development to drug discovery, mechanism-of-action studies, animal physiology, and translational research. Trainees gain experience with cutting-edge technologies including automated electrophysiology, high-throughput screening, medicinal chemistry, molecular pharmacology, and advanced physiological models.

Our alumni and trainees develop a unique combination of quantitative, experimental, and translational research skills that are increasingly sought after in both academia and industry. Whether your goal is to lead an independent academic laboratory, drive therapeutic innovation in biotechnology or pharmaceutical companies, or pursue careers at the intersection of science and medicine, training in the Denton Laboratory provides an exceptional foundation for a high-impact scientific career.

We are always interested in recruiting outstanding graduate students, postdoctoral fellows, and collaborators who are excited about discovering new biology, developing first-in-class molecular probes, and translating ion channel science into transformative therapeutics. Here, fundamental discovery and drug development are not separate pursuits; they are part of the same mission to improve human health through innovative science.
Research Keywords
ion channels, potassium channels, chloride channels, lysosomal ion channels, therapeutic development, molecular pharmacology, structure-function analysis, high-throughput screening, electrophysiology, kidney, metabolic, hypertension, neurological, autism, schizophrenia, Parkinson's Disease
Publications
Li K, Le SD, Satpute Janve V, Lazarenko RM, Romaine IM, Kim K, Sulikowski GA, Waterson AG, Denton JS. A nonhydrolyzable candesartan cilexetil analog reveals synergistic activation as a tractable mechanism for TMEM175 modulation. Am J Physiol Cell Physiol [print-electronic]. 2026 Aug 8/1/2026; 331(2): C415-C424-C424. PMID: 42389983, DOI: 10.1152/ajpcell.00348.2026, ISSN: 1522-1563.

Spearing PK, Satpute Janke V, Romaine IM, Jayakodiarachchi N, Guttentag BW, Jana S, Kim K, Denton JS, Lindsley CW, Waterson AG. Optimization of Pyrazole-Based Activators of Kv3.1. ACS Med Chem Lett. 2026 Jul 7/9/2026; 17(7): 1655-63. PMID: 42445039, PMCID: PMC13358987, DOI: 10.1021/acsmedchemlett.6c00272, ISSN: 1948-5875.

Chandrappa RU, Satpute Janve V, Days EL, Denton JS. Discovery of Kv3.1 channel inhibitors reveals VU0521426 as a state-dependent inactivator preferentially active against pathogenic gain-of-function mutants. Am J Physiol Cell Physiol [print-electronic]. 2026 Jun 6/1/2026; 330(6): C1788-C1799-C1799. PMID: 42141755, PMCID: PMC13270922, DOI: 10.1152/ajpcell.00239.2026, ISSN: 1522-1563.

Li K, Satpute Janve V, Le SD, Days EL, Bauer JA, Lazarenko RM, Gulsevin A, Denton JS. Activation of TMEM175 lysosomal ion channels by CysLT1 receptor antagonists. Am J Physiol Cell Physiol [print-electronic]. 2026 Apr 4/1/2026; 330(4): C715-C726-C726. PMID: 41670588, DOI: 10.1152/ajpcell.00951.2025, ISSN: 1522-1563.

Bouchard JL, de Andrade Horn P, Nishio Y, Days EL, Li L, Lazarenko RM, Sant S, Chang S, Bauer JA, Denton JS, Boutaud O, Abe M, Lindsley CW. Identification of Kir2.1 Inhibitors from a High-Throughput Screen. Assay Drug Dev Technol [print-electronic]. 2026 Apr; 24(3): 265-73. PMID: 41701551, DOI: 10.1177/1540658X261415763, ISSN: 1557-8127.

Nakhe AY, Dobson JR, Dadi PK, Westover D, Days EL, Vinson P, Weaver CD, Denton JS, Peachee SJ, Behera S, Gibson SE, Rodriguez Da Silva VA, Sela A, Dickerson MT, Jacobson DA. Identification of potent and selective small molecule TALK-1 inhibitors that promote ß-cell function. Mol Pharmacol [print-electronic]. 2026; 108(5-6): 100130. PMID: 42269513, PII: S0026-895X(26)00030-1, DOI: 10.1016/j.molpha.2026.100130, ISSN: 1521-0111.

Tanaka M, Sekioka Y, Hashimoto G, Mori T, Shono T, Isaji Y, Hisaichi K, Childress ES, Bollinger S, Schmitt JA, Chopko TC, Garrison AT, Perry CK, Chronister K, Kramer M, Chang S, Watson KJ, Dickerson JW, Bubser M, Rook JM, Jones CK, Boutaud O, Bridges TM, Denton JS, Engers DW, Kurata H, Lindsley CW. Optimization of Selective and CNS Penetrant Alkyne-Based TREK Inhibitors: The Discovery and Characterization of ONO-9517601 (VU6022856) and ONO-7927846 (VU6024391). J Med Chem [print-electronic]. 2025 Nov 11/13/2025; 68(21): 23554-72. PMID: 41104520, PMCID: PMC12621189, DOI: 10.1021/acs.jmedchem.5c02535, ISSN: 1520-4804.

Wu A, Inoue MK, Zhang Y, Hasenour CM, Arroyo JP, Bock F, Yu A, Ferdaus MZ, Blackwell Y, Lazarenko RM, Young JD, Denton JS, Delpire E, Zhang MZ, Harris RC, Terker AS. Kir5.1-modulated potassium flux stimulates an anabolic kidney phenotype. IScience. 2025 Oct 10/17/2025; 28(10): 113601. PMID: 41111916, PMCID: PMC12529358, PII: S2589-0042(25)01862-0, DOI: 10.1016/j.isci.2025.113601, ISSN: 2589-0042.

Yamada T, Bisignano P, Karakas E, Denton JS. A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs. Commun Biol. 2025 Oct 10/6/2025; 8(1): 1432. PMID: 41053296, PMCID: PMC12501385, PII: 10.1038/s42003-025-08795-1, DOI: 10.1038/s42003-025-08795-1, ISSN: 2399-3642.

Temple KJ, Li P, McKinnie HG, Thompson Gray A, Bertron JL, Ringuette AE, de Andrade Horn P, Lyon MD, Bhagwat S, Asadi L, Li S, Lazarenko RM, McCarthy R, Chang S, Turkett JA, Kramlinger V, Watson KJ, Zagol-Ikapitte IA, Denton JS, Santi CM, Jones CK, Lindsley CW, Boutaud O. Highly Potent and Subtype-Selective Sperm-Specific Potassium Channel SLO3 Inhibitors Display High Tissue Exposure in the Murine Female Reproductive Tract. ACS Pharmacol Transl Sci. 2025 Sep 9/12/2025; 8(9): 3281-95. PMID: 40969884, PMCID: PMC12441834, DOI: 10.1021/acsptsci.5c00416, ISSN: 2575-9108.

Duncan RA, Haymer DH, Lazarenko RM, Li L, Blackwell Y, Days EL, Krishnan S, Gray AT, Boutaud O, Engers DW, Lindsley CW, Denton JS, Bender AM. Characterization of Next-Generation Inhibitors for the Inward-Rectifier Potassium Channel Kir2.1: Discovery of VU6080824. ACS Med Chem Lett. 2025 Sep 9/11/2025; 16(9): 1762-71. PMID: 40959251, PMCID: PMC12434521, DOI: 10.1021/acsmedchemlett.5c00297, ISSN: 1948-5875.

Karakas E, Strange K, Denton JS. Recent advances in structural characterization of volume-regulated anion channels (VRACs). J Physiol [print-electronic]. 2025 Aug; 603(15): 4201-11. PMID: 39977537, PMCID: PMC12333906, DOI: 10.1113/JP286189, ISSN: 1469-7793.

Li K, Janve VS, Denton JS. Automated patch clamp analysis of heterologously expressed Kir6.2/SUR1 and Kir6.1/SUR2B KATP currents. Am J Physiol Cell Physiol [print-electronic]. 2025 Jul 7/1/2025; 329(1): C82-C92-C92. PMID: 40465479, PMCID: PMC12191713, DOI: 10.1152/ajpcell.00266.2025, ISSN: 1522-1563.

Tanaka M, Mori T, Hashimoto G, Mitsui K, Kishi A, Childress ES, Bollinger SR, Chopko TC, Bridges TM, Stafford DG, Huang Z, Wolf MA, Engers DW, Denton JS, Kurata H, Lindsley CW. Discovery of ONO-TR-772 (VU6018042): A Highly Selective and CNS Penetrant TREK Inhibitor in Vivo Tool Compound. ACS Med Chem Lett. 2025 May 5/8/2025; 16(5): 896-901. PMID: 40365404, PMCID: PMC12067145, DOI: 10.1021/acsmedchemlett.5c00215, ISSN: 1948-5875.

Yashiro K, Iwaki Y, Urata H, Kokubo M, Mori T, Sekioka Y, Isami K, Kato J, Wieting J, McGowan KM, Bridges TM, Boutaud O, Engers DW, Denton JS, Kurata H, Lindsley CW. Discovery of ONO-2920632 (VU6011887): A Highly Selective and CNS Penetrant TREK-2 (TWIK-Related K+ Channel 2) Preferring Activator In Vivo Tool Compound. ACS Chem Neurosci [print-electronic]. 2025 Mar 3/5/2025; 16(5): 960-7. PMID: 39981749, PMCID: PMC11887051, DOI: 10.1021/acschemneuro.5c00032, ISSN: 1948-7193.

Denton JS. Dam antidepressants. Nat Chem Biol. 2024 Jul; 20(7): 803-4. PMID: 38454073, PII: 10.1038/s41589-024-01567-8, DOI: 10.1038/s41589-024-01567-8, ISSN: 1552-4469.

Zhang Y, Bock F, Ferdaus M, Arroyo JP, L Rose K, Patel P, Denton JS, Delpire E, Weinstein AM, Zhang MZ, Harris RC, Terker AS. Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2. Nat Commun. 2024 Jun 6/17/2024; 15(1): 5144. PMID: 38886379, PMCID: PMC11183202, PII: 10.1038/s41467-024-49562-w, DOI: 10.1038/s41467-024-49562-w, ISSN: 2041-1723.

Li K, McClenahan SJ, Han C, Bungard JD, Rathnayake U, Boutaud O, Bauer JA, Days EL, Lindsley CW, Shelton EL, Denton JS. Discovery and Characterization of VU0542270, the First Selective Inhibitor of Vascular Kir6.1/SUR2B KATP Channels. Mol Pharmacol. 2024 Feb 2/15/2024; 105(3): 202-12. PMID: 38302135, PMCID: PMC10877733, PII: S0026-895X(24)00098-1, DOI: 10.1124/molpharm.123.000783, ISSN: 1521-0111.

Zietara A, Palygin O, Levchenko V, Dissanayake LV, Klemens CA, Geurts A, Denton JS, Staruschenko A. Kir7.1 knockdown and inhibition alter renal electrolyte handling but not the development of hypertension in Dahl salt-sensitive rats. Am J Physiol Renal Physiol [print-electronic]. 2023 Aug 8/1/2023; 325(2): F177-F187-F187. PMID: 37318990, PMCID: PMC10393338, DOI: 10.1152/ajprenal.00059.2023, ISSN: 1522-1466.

Dodd CJ, Chronister KS, Rathnayake U, Parr LC, Li K, Chang S, Mi D, Days EL, Bauer JA, Cho HP, Boutaud O, Denton JS, Lindsley CW, Han C. Synthesis and SAR of a novel Kir6.2/SUR1 channel opener scaffold identified by HTS. Bioorg Med Chem Lett [print-electronic]. 2023 May 5/1/2023; 87: 129256. PMID: 36966977, PMCID: PMC10395071, PII: S0960-894X(23)00134-8, DOI: 10.1016/j.bmcl.2023.129256, ISSN: 1464-3405.

Takahashi H, Yamada T, Denton JS, Strange K, Karakas E. Cryo-EM structures of an LRRC8 chimera with native functional properties reveal heptameric assembly. Elife. 2023 Mar 3/10/2023; 12: PMID: 36897307, PMCID: PMC10049205, PII: 82431, DOI: 10.7554/eLife.82431, ISSN: 2050-084X.

Denton JS, Delpire E. Special collection on inward rectifying K+ channels [editorial]. Am J Physiol Cell Physiol [print-electronic]. 2023 Mar 3/1/2023; 324(3): C603-C605-C605. PMID: 36689674, PMCID: PMC9942886, DOI: 10.1152/ajpcell.00457.2022, ISSN: 1522-1563.

Terker AS, Zhang Y, Arroyo JP, Cao S, Wang S, Fan X, Denton JS, Zhang MZ, Harris RC. Kir4.2 mediates proximal potassium effects on glutaminase activity and kidney injury. Cell Rep. 2022 Dec 12/20/2022; 41(12): 111840. PMID: 36543132, PMCID: PMC9827473, PII: S2211-1247(22)01732-6, DOI: 10.1016/j.celrep.2022.111840, ISSN: 2211-1247.

Figueroa EE, Denton JS. A SWELL time to develop the molecular pharmacology of the volume-regulated anion channel (VRAC). Channels (Austin). 2022 Dec; 16(1): 27-36. PMID: 35114895, PMCID: PMC8820792, DOI: 10.1080/19336950.2022.2033511, ISSN: 1933-6969.

Isaeva E, Bohovyk R, Fedoriuk M, Shalygin A, Klemens CA, Zietara A, Levchenko V, Denton JS, Staruschenko A, Palygin O. Crosstalk between epithelial sodium channels (ENaC) and basolateral potassium channels (Kir 4.1/Kir 5.1) in the cortical collecting duct. Br J Pharmacol [print-electronic]. 2022 Jun; 179(12): 2953-68. PMID: 34904226, PMCID: PMC9106811, DOI: 10.1111/bph.15779, ISSN: 1476-5381.

McClenahan SJ, Kent CN, Kharade SV, Isaeva E, Williams JC, Han C, Terker A, Gresham R, Lazarenko RM, Days EL, Romaine IM, Bauer JA, Boutaud O, Sulikowski GA, Harris R, Weaver CD, Staruschenko A, Lindsley CW, Denton JS. VU6036720: The First Potent and Selective In Vitro Inhibitor of Heteromeric Kir4.1/5.1 Inward Rectifier Potassium Channels. Mol Pharmacol [print-electronic]. 2022 May; 101(5): 357-70. PMID: 35246480, PMCID: PMC9092466, PII: S0026-895X(24)01228-8, DOI: 10.1124/molpharm.121.000464, ISSN: 1521-0111.

Piermarini PM, Denton JS, Swale DR. The Molecular Physiology and Toxicology of Inward Rectifier Potassium Channels in Insects. Annu Rev Entomol [print-electronic]. 2022 Jan 1/7/2022; 67: 125-42. PMID: 34606365, DOI: 10.1146/annurev-ento-062121-063338, ISSN: 1545-4487.

Figueroa EE, Denton JS. Zinc pyrithione activates the volume-regulated anion channel through an antioxidant-sensitive mechanism. Am J Physiol Cell Physiol [print-electronic]. 2021 Jun 6/1/2021; 320(6): C1088-C1098-C1098. PMID: 33826406, PMCID: PMC8285639, DOI: 10.1152/ajpcell.00070.2021, ISSN: 1522-1563.

Weaver CD, Denton JS. Next-generation inward rectifier potassium channel modulators: discovery and molecular pharmacology. Am J Physiol Cell Physiol [print-electronic]. 2021 Jun 6/1/2021; 320(6): C1125-C1140-C1140. PMID: 33826405, PMCID: PMC8285633, DOI: 10.1152/ajpcell.00548.2020, ISSN: 1522-1563.

Yamada T, Figueroa EE, Denton JS, Strange K. LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology. Am J Physiol Cell Physiol [print-electronic]. 2021 Mar 3/1/2021; 320(3): C293-C303-C303. PMID: 33356947, PMCID: PMC8294627, DOI: 10.1152/ajpcell.00454.2020, ISSN: 1522-1563.

Aretz CD, Kharade SV, Chronister K, Rusconi Trigueros R, Martinez Rodriguez EJ, Piermarini PM, Denton JS, Hopkins CR. Further SAR on the (Phenylsulfonyl)piperazine Scaffold as Inhibitors of the Aedes aegypti Kir1 (AeKir) Channel and Larvicides. ChemMedChem [print-electronic]. 2021 Jan 1/19/2021; 16(2): 319-27. PMID: 32926544, PMCID: PMC7856040, DOI: 10.1002/cmdc.202000598, ISSN: 1860-7187.

Zaborska KE, Dadi PK, Dickerson MT, Nakhe AY, Thorson AS, Schaub CM, Graff SM, Stanley JE, Kondapavuluru RS, Denton JS, Jacobson DA. Lactate activation of a-cell KATP channels inhibits glucagon secretion by hyperpolarizing the membrane potential and reducing Ca2+ entry. Mol Metab [print-electronic]. 2020 Dec; 42: 101056. PMID: 32736089, PMCID: PMC7479281, PII: S2212-8778(20)30130-7, DOI: 10.1016/j.molmet.2020.101056, ISSN: 2212-8778.

Spitznagel BD, Mishra NM, Qunies AM, Prael FJ, Du Y, Kozek KA, Lazarenko RM, Denton JS, Emmitte KA, Weaver CD. VU0606170, a Selective Slack Channels Inhibitor, Decreases Calcium Oscillations in Cultured Cortical Neurons. ACS Chem Neurosci [print-electronic]. 2020 Nov 11/4/2020; 11(21): 3658-71. PMID: 33143429, DOI: 10.1021/acschemneuro.0c00583, ISSN: 1948-7193.

Afzal A, Figueroa EE, Kharade SV, Bittman K, Matlock BK, Flaherty DK, Denton JS. The LRRC8 volume-regulated anion channel inhibitor, DCPIB, inhibits mitochondrial respiration independently of the channel. Physiol Rep. 2019 Dec; 7(23): e14303. PMID: 31814333, PMCID: PMC6900491, DOI: 10.14814/phy2.14303, ISSN: 2051-817X.

Figueroa EE, Kramer M, Strange K, Denton JS. CysLT1 receptor antagonists pranlukast and zafirlukast inhibit LRRC8-mediated volume regulated anion channels independently of the receptor. Am J Physiol Cell Physiol [print-electronic]. 2019 Oct 10/1/2019; 317(4): C857-C866-C866. PMID: 31390227, PMCID: PMC6850990, DOI: 10.1152/ajpcell.00281.2019, ISSN: 1522-1563.

Kharade SV, Sanchez-Andres JV, Fulton MG, Shelton EL, Blobaum AL, Engers DW, Hofmann CS, Dadi PK, Lantier L, Jacobson DA, Lindsley CW, Denton JS. Structure-Activity Relationships, Pharmacokinetics, and Pharmacodynamics of the Kir6.2/SUR1-Specific Channel Opener VU0071063. J Pharmacol Exp Ther [print-electronic]. 2019 Sep; 370(3): 350-9. PMID: 31201216, PMCID: PMC6691189, PII: S0022-3565(24)26070-5, DOI: 10.1124/jpet.119.257204, ISSN: 1521-0103.

Iwaki Y, Yashiro K, Kokubo M, Mori T, Wieting JM, McGowan KM, Bridges TM, Engers DW, Denton JS, Kurata H, Lindsley CW. Towards a TREK-1/2 (TWIK-Related K+ Channel 1 and 2) dual activator tool compound: Multi-dimensional optimization of BL-1249 [letter]. Bioorg Med Chem Lett [print-electronic]. 2019 Jul 7/1/2019; 29(13): 1601-4. PMID: 31072652, PII: S0960-894X(19)30282-3, DOI: 10.1016/j.bmcl.2019.04.048, ISSN: 1464-3405.

Aretz CD, Morwitzer MJ, Sanford AG, Hogan AM, Portillo MV, Kharade SV, Kramer M, McCarthey JB, Trigueros RR, Piermarini PM, Denton JS, Hopkins CR. Discovery and Characterization of 2-Nitro-5-(4-(phenylsulfonyl)piperazin-1-yl)- N-(pyridin-4-ylmethyl)anilines as Novel Inhibitors of the Aedes aegypti Kir1 ( AeKir1) Channel. ACS Infect Dis [print-electronic]. 2019 Jun 6/14/2019; 5(6): 917-31. PMID: 30832472, PMCID: PMC7241282, DOI: 10.1021/acsinfecdis.8b00368, ISSN: 2373-8227.

Strange K, Yamada T, Denton JS. A 30-year journey from volume-regulated anion currents to molecular structure of the LRRC8 channel. J Gen Physiol [print-electronic]. 2019 Feb 2/4/2019; 151(2): 100-17. PMID: 30651298, PMCID: PMC6363415, PII: jgp.201812138, DOI: 10.1085/jgp.201812138, ISSN: 1540-7748.

Kozek KA, Du Y, Sharma S, Prael FJ, Spitznagel BD, Kharade SV, Denton JS, Hopkins CR, Weaver CD. Discovery and Characterization of VU0529331, a Synthetic Small-Molecule Activator of Homomeric G Protein-Gated, Inwardly Rectifying, Potassium (GIRK) Channels. ACS Chem Neurosci [print-electronic]. 2019 Jan 1/16/2019; 10(1): 358-70. PMID: 30136838, PMCID: PMC6528656, DOI: 10.1021/acschemneuro.8b00287, ISSN: 1948-7193.

Carrington SJ, Hernandez CC, Swale DR, Aluko OA, Denton JS, Cone RD. G protein-coupled receptors differentially regulate glycosylation and activity of the inwardly rectifying potassium channel Kir7.1. J Biol Chem [print-electronic]. 2018 Nov 11/16/2018; 293(46): 17739-53. PMID: 30257863, PMCID: PMC6240878, PII: S0021-9258(20)31232-1, DOI: 10.1074/jbc.RA118.003238, ISSN: 1083-351X.

Rusconi Trigueros R, Hopkins CR, Denton JS, Piermarini PM. Pharmacological Inhibition of Inward Rectifier Potassium Channels Induces Lethality in Larval Aedes aegypti. Insects. 2018 Nov 11/15/2018; 9(4): PMID: 30445675, PMCID: PMC6315791, PII: insects9040163, DOI: 10.3390/insects9040163, ISSN: 2075-4450.

Piermarini PM, Inocente EA, Acosta N, Hopkins CR, Denton JS, Michel AP. Inward rectifier potassium (Kir) channels in the soybean aphid Aphis glycines: Functional characterization, pharmacology, and toxicology. J Insect Physiol [print-electronic]. 2018 Oct; 110: 57-65. PMID: 30196125, PMCID: PMC6173977, PII: S0022-1910(18)30291-9, DOI: 10.1016/j.jinsphys.2018.09.001, ISSN: 1879-1611.

Kharade SV, Kurata H, Bender AM, Blobaum AL, Figueroa EE, Duran A, Kramer M, Days E, Vinson P, Flores D, Satlin LM, Meiler J, Weaver CD, Lindsley CW, Hopkins CR, Denton JS. Discovery, Characterization, and Effects on Renal Fluid and Electrolyte Excretion of the Kir4.1 Potassium Channel Pore Blocker, VU0134992. Mol Pharmacol [print-electronic]. 2018 Aug; 94(2): 926-37. PMID: 29895592, PMCID: PMC6041953, PII: S0026-895X(24)00791-0, DOI: 10.1124/mol.118.112359, ISSN: 1521-0111.

Sammons MF, Kharade SV, Filipski KJ, Boehm M, Smith AC, Shavnya A, Fernando DP, Dowling MS, Carpino PA, Castle NA, Zellmer SG, Antonio BM, Gosset JR, Carlo A, Denton JS. Discovery and in Vitro Optimization of 3-Sulfamoylbenzamides as ROMK Inhibitors. ACS Med Chem Lett. 2018 Feb 2/8/2018; 9(2): 125-30. PMID: 29456800, PMCID: PMC5807870, DOI: 10.1021/acsmedchemlett.7b00481, ISSN: 1948-5875.

Denton JS, Kharade SV. Plight of the pore polar bar(rier). Channels (Austin) [print-electronic]. 2017 Nov 11/2/2017; 11(6): 502-3. PMID: 28806132, PMCID: PMC5786191, DOI: 10.1080/19336950.2017.1367234, ISSN: 1933-6969.

Kharade SV, Sheehan JH, Figueroa EE, Meiler J, Denton JS. Pore Polarity and Charge Determine Differential Block of Kir1.1 and Kir7.1 Potassium Channels by Small-Molecule Inhibitor VU590. Mol Pharmacol [print-electronic]. 2017 Sep; 92(3): 338-46. PMID: 28619748, PMCID: PMC5553192, PII: S0026-895X(24)00647-3, DOI: 10.1124/mol.117.108472, ISSN: 1521-0111.

Yang Z, Statler BM, Calkins TL, Alfaro E, Esquivel CJ, Rouhier MF, Denton JS, Piermarini PM. Dynamic expression of genes encoding subunits of inward rectifier potassium (Kir) channels in the yellow fever mosquito Aedes aegypti. Comp Biochem Physiol B Biochem Mol Biol [print-electronic]. 2017 Feb; 204: 35-44. PMID: 27836744, PII: S1096-4959(16)30159-2, DOI: 10.1016/j.cbpb.2016.11.003, ISSN: 1879-1107.

Piermarini PM, Esquivel CJ, Denton JS. Malpighian Tubules as Novel Targets for Mosquito Control. Int J Environ Res Public Health. 2017 Jan 1/24/2017; 14(2): PMID: 28125032, PMCID: PMC5334665, PII: ijerph14020111, DOI: 10.3390/ijerph14020111, ISSN: 1660-4601.

Swale DR, Engers DW, Bollinger SR, Gross A, Inocente EA, Days E, Kanga F, Johnson RM, Yang L, Bloomquist JR, Hopkins CR, Piermarini PM, Denton JS. An insecticide resistance-breaking mosquitocide targeting inward rectifier potassium channels in vectors of Zika virus and malaria. Sci Rep. 2016 Nov 11/16/2016; 6: 36954. PMID: 27849039, PMCID: PMC5111108, PII: srep36954, DOI: 10.1038/srep36954, ISSN: 2045-2322.

Martin GM, Rex EA, Devaraneni P, Denton JS, Boodhansingh KE, DeLeon DD, Stanley CA, Shyng SL. Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations. J Biol Chem [print-electronic]. 2016 Oct 10/14/2016; 291(42): 21971-83. PMID: 27573238, PMCID: PMC5063981, PII: S0021-9258(20)35781-1, DOI: 10.1074/jbc.M116.749366, ISSN: 1083-351X.

Swale DR, Kurata H, Kharade SV, Sheehan J, Raphemot R, Voigtritter KR, Figueroa EE, Meiler J, Blobaum AL, Lindsley CW, Hopkins CR, Denton JS. ML418: The First Selective, Sub-Micromolar Pore Blocker of Kir7.1 Potassium Channels. ACS Chem Neurosci [print-electronic]. 2016 Jul 7/20/2016; 7(7): 1013-23. PMID: 27184474, PMCID: PMC5131535, DOI: 10.1021/acschemneuro.6b00111, ISSN: 1948-7193.

Kharade SV, Nichols C, Denton JS. The shifting landscape of KATP channelopathies and the need for 'sharper' therapeutics. Future Med Chem [print-electronic]. 2016 May; 8(7): 789-802. PMID: 27161588, PMCID: PMC4976861, DOI: 10.4155/fmc-2016-0005, ISSN: 1756-8927.

Kharade SV, Flores D, Lindsley CW, Satlin LM, Denton JS. ROMK inhibitor actions in the nephron probed with diuretics. Am J Physiol Renal Physiol [print-electronic]. 2016 Apr 4/15/2016; 310(8): F732-F737-F737. PMID: 26661652, PMCID: PMC4835929, PII: ajprenal.00423.2015, DOI: 10.1152/ajprenal.00423.2015, ISSN: 1522-1466.

Piermarini PM, Dunemann SM, Rouhier MF, Calkins TL, Raphemot R, Denton JS, Hine RM, Beyenbach KW. Localization and role of inward rectifier K(+) channels in Malpighian tubules of the yellow fever mosquito Aedes aegypti. Insect Biochem Mol Biol [print-electronic]. 2015 Dec; 67: 59-73. PMID: 26079629, PII: S0965-1748(15)30009-6, DOI: 10.1016/j.ibmb.2015.06.006, ISSN: 1879-0240.

Ghamari-Langroudi M, Digby GJ, Sebag JA, Millhauser GL, Palomino R, Matthews R, Gillyard T, Panaro BL, Tough IR, Cox HM, Denton JS, Cone RD. G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons. Nature [print-electronic]. 2015 Apr 4/2/2015; 520(7545): 94-8. PMID: 25600267, PMCID: PMC4383680, PII: nature14051, DOI: 10.1038/nature14051, ISSN: 1476-4687.

Swale DR, Sheehan JH, Banerjee S, Husni AS, Nguyen TT, Meiler J, Denton JS. Computational and functional analyses of a small-molecule binding site in ROMK. Biophys J. 2015 Mar 3/10/2015; 108(5): 1094-103. PMID: 25762321, PMCID: PMC4375722, PII: S0006-3495(15)00116-2, DOI: 10.1016/j.bpj.2015.01.022, ISSN: 1542-0086.

Herington JL, Swale DR, Brown N, Shelton EL, Choi H, Williams CH, Hong CC, Paria BC, Denton JS, Reese J. High-Throughput Screening of Myometrial Calcium-Mobilization to Identify Modulators of Uterine Contractility. PLoS One. 2015; 10(11): e0143243. PMID: 26600013, PMCID: PMC4658040, PII: PONE-D-15-12311, DOI: 10.1371/journal.pone.0143243, ISSN: 1932-6203.

Kharade SV, Swale DR, Denton JS. ROMK (Kir1.1) pharmacology comes of age. Channels (Austin). 2015; 9(3): 119-20. PMID: 25941772, PMCID: PMC4594458, DOI: 10.1080/19336950.2015.1046733, ISSN: 1933-6969.

McCloskey C, Rada C, Bailey E, McCavera S, van den Berg HA, Atia J, Rand DA, Shmygol A, Chan YW, Quenby S, Brosens JJ, Vatish M, Zhang J, Denton JS, Taggart MJ, Kettleborough C, Tickle D, Jerman J, Wright P, Dale T, Kanumilli S, Trezise DJ, Thornton S, Brown P, Catalano R, Lin N, England SK, Blanks AM. The inwardly rectifying K+ channel KIR7.1 controls uterine excitability throughout pregnancy. EMBO Mol Med. 2014 Sep; 6(9): 1161-74. PMID: 25056913, PMCID: PMC4197863, PII: emmm.201403944, DOI: 10.15252/emmm.201403944, ISSN: 1757-4684.

Raphemot R, Estévez-Lao TY, Rouhier MF, Piermarini PM, Denton JS, Hillyer JF. Molecular and functional characterization of Anopheles gambiae inward rectifier potassium (Kir1) channels: a novel role in egg production. Insect Biochem Mol Biol [print-electronic]. 2014 Aug; 51: 10-9. PMID: 24855023, PMCID: PMC4121989, PII: S0965-1748(14)00078-2, DOI: 10.1016/j.ibmb.2014.05.002, ISSN: 1879-0240.

Raphemot R, Swale DR, Dadi PK, Jacobson DA, Cooper P, Wojtovich AP, Banerjee S, Nichols CG, Denton JS. Direct activation of ß-cell KATP channels with a novel xanthine derivative. Mol Pharmacol [print-electronic]. 2014 Jun; 85(6): 858-65. PMID: 24646456, PMCID: PMC4014665, PII: S0026-895X(24)03929-4, DOI: 10.1124/mol.114.091884, ISSN: 1521-0111.

Denton JS. Druggability of the inward rectifier family: a hope for rare channelopathies? [editorial]. Future Med Chem [print-electronic]. 2014 Jun; 6(9): 971-3. PMID: 24547691, DOI: 10.4155/fmc.14.12, ISSN: 1756-8927.

Swale DR, Kharade SV, Denton JS. Cardiac and renal inward rectifier potassium channel pharmacology: emerging tools for integrative physiology and therapeutics. Curr Opin Pharmacol [print-electronic]. 2014 Apr; 15: 7-15. PMID: 24721648, PMCID: PMC4097192, PII: S1471-4892(13)00218-X, DOI: 10.1016/j.coph.2013.11.002, ISSN: 1471-4973.

Raphemot R, Rouhier MF, Swale DR, Days E, Weaver CD, Lovell KM, Konkel LC, Engers DW, Bollinger SR, Hopkins C, Piermarini PM, Denton JS. Discovery and characterization of a potent and selective inhibitor of Aedes aegypti inward rectifier potassium channels. PLoS One. 2014; 9(11): e110772. PMID: 25375326, PMCID: PMC4222822, PII: PONE-D-14-24567, DOI: 10.1371/journal.pone.0110772, ISSN: 1932-6203.

Rouhier MF, Raphemot R, Denton JS, Piermarini PM. Pharmacological validation of an inward-rectifier potassium (Kir) channel as an insecticide target in the yellow fever mosquito Aedes aegypti. PLoS One. 2014; 9(6): e100700. PMID: 24959745, PMCID: PMC4069099, PII: PONE-D-14-17901, DOI: 10.1371/journal.pone.0100700, ISSN: 1932-6203.

Bruehl S, Denton JS, Lonergan D, Koran ME, Chont M, Sobey C, Fernando S, Bush WS, Mishra P, Thornton-Wells TA. Associations between KCNJ6 (GIRK2) gene polymorphisms and pain-related phenotypes. Pain [print-electronic]. 2013 Dec; 154(12): 2853-9. PMID: 23994450, PMCID: PMC3845348, PII: 00006396-201312000-00037, DOI: 10.1016/j.pain.2013.08.026, ISSN: 1872-6623.

Denton JS, Pao AC, Maduke M. Novel diuretic targets. Am J Physiol Renal Physiol [print-electronic]. 2013 Oct 10/1/2013; 305(7): F931-42-F942. PMID: 23863472, PMCID: PMC3798746, PII: ajprenal.00230.2013, DOI: 10.1152/ajprenal.00230.2013, ISSN: 1522-1466.

Raphemot R, Weaver CD, Denton JS. High-throughput screening for small-molecule modulators of inward rectifier potassium channels. J Vis Exp. 2013 Jan 1/27/2013; (71): PMID: 23381507, PMCID: PMC3582647, PII: 4209, DOI: 10.3791/4209, ISSN: 1940-087X.

Raphemot R, Kadakia RJ, Olsen ML, Banerjee S, Days E, Smith SS, Weaver CD, Denton JS. Development and validation of fluorescence-based and automated patch clamp-based functional assays for the inward rectifier potassium channel Kir4.1. Assay Drug Dev Technol [print-electronic]. 2013; 11(9-10): 532-43. PMID: 24266659, PMCID: PMC3870600, DOI: 10.1089/adt.2013.544, ISSN: 1557-8127.

Raphemot R, Rouhier MF, Hopkins CR, Gogliotti RD, Lovell KM, Hine RM, Ghosalkar D, Longo A, Beyenbach KW, Denton JS, Piermarini PM. Eliciting renal failure in mosquitoes with a small-molecule inhibitor of inward-rectifying potassium channels. PLoS One [electronic-print]. 2013; 8(5): e64905. PMID: 23734226, PMCID: PMC3666979, PII: PONE-D-13-12458, DOI: 10.1371/journal.pone.0064905, ISSN: 1932-6203.

Denton JS, Jacobson DA. Channeling dysglycemia: ion-channel variations perturbing glucose homeostasis. Trends Endocrinol Metab [print-electronic]. 2012 Jan; 23(1): 41-8. PMID: 22134088, PMCID: PMC3733341, PII: S1043-2760(11)00152-4, DOI: 10.1016/j.tem.2011.09.004, ISSN: 1879-3061.

Raphemot R, Lonergan DF, Nguyen TT, Utley T, Lewis LM, Kadakia R, Weaver CD, Gogliotti R, Hopkins C, Lindsley CW, Denton JS. Discovery, characterization, and structure-activity relationships of an inhibitor of inward rectifier potassium (Kir) channels with preference for Kir2.3, Kir3.x, and Kir7.1. Front Pharmacol. 2011; 2: 75. PMID: 22275899, PMCID: PMC3254186, DOI: 10.3389/fphar.2011.00075, ISSN: 1663-9812.

Bhave G, Chauder BA, Liu W, Dawson ES, Kadakia R, Nguyen TT, Lewis LM, Meiler J, Weaver CD, Satlin LM, Lindsley CW, Denton JS. Development of a selective small-molecule inhibitor of Kir1.1, the renal outer medullary potassium channel. Mol Pharmacol [print-electronic]. 2011 Jan; 79(1): 42-50. PMID: 20926757, PMCID: PMC3014278, PII: S0026-895X(24)02856-6, DOI: 10.1124/mol.110.066928, ISSN: 1521-0111.

Bhave G, Lonergan D, Chauder BA, Denton JS. Small-molecule modulators of inward rectifier K+ channels: recent advances and future possibilities. Future Med Chem. 2010 May; 2(5): 757-74. PMID: 20543968, PMCID: PMC2883187, DOI: 10.4155/fmc.10.179, ISSN: 1756-8927.

Lewis LM, Bhave G, Chauder BA, Banerjee S, Lornsen KA, Redha R, Fallen K, Lindsley CW, Weaver CD, Denton JS. High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1. Mol Pharmacol [print-electronic]. 2009 Nov; 76(5): 1094-103. PMID: 19706730, PMCID: PMC2774996, PII: S0026-895X(24)02079-0, DOI: 10.1124/mol.109.059840, ISSN: 1521-0111.

Fallen K, Banerjee S, Sheehan J, Addison D, Lewis LM, Meiler J, Denton JS. The Kir channel immunoglobulin domain is essential for Kir1.1 (ROMK) thermodynamic stability, trafficking and gating. Channels (Austin) [print-electronic]. 2009; 3(1): 57-68. PMID: 19221509, PMCID: PMC7968143, PII: 7817, DOI: 10.4161/chan.3.1.7817, ISSN: 1933-6969.

Denton JS, Leiter JC. Anomalous effects of external TEA on permeation and gating of the A-type potassium current in H. aspersa neuronal somata. J Membr Biol. 2002 Nov 11/1/2002; 190(1): 17-28. PMID: 12422269, DOI: 10.1007/s00232-002-1021-9, ISSN: 0022-2631.