The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke
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Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. The voltage-gated proton channel Hv1 enables NOX function by compensating cellular loss of electrons with protons. Accordingly, we investigated whether NOX-mediated brain damage in stroke can be inhibited by suppression of Hv1. We found that mouse and human brain microglia, but not neurons or astrocytes, expressed large Hv1-mediated currents. Hv1 was required for NOX-dependent ROS generation in brain microglia in situ and in vivo. Mice lacking Hv1 were protected from NOX-mediated neuronal death and brain damage 24 h after stroke. These results indicate that Hv1-dependent ROS production is responsible for a substantial fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke.
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Dihydroethidium oxidation to ethidium is specific to O2.- and binds to DNA and RNA of O2.-producing cells.
“Cellular production of reactive oxygen species (ROS) in brain slices was visualised through the O2.-specific oxidation of dihydroethidium to ethidium, which binds to the DNA and RNA of O2.-producing cells (46).”
From Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes (2019) · cites this paper as [46]
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Cites
Reversible middle cerebral artery occlusion without craniectomy in rats.
Longa, E. Z., Weinstein, P. R., Carlson, S., & Cummins, R. (1989) · Stroke · doi:10.1161/01.str.20.1.84 · Cited by 7,463 · see citing works
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · see citing works
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110 · see citing works
ATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913 · see citing works
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · see citing works
The immunology of stroke: from mechanisms to translation
Iadecola, C., & Anrather, J. (2011) · Nature Medicine · doi:10.1038/nm.2399 · Cited by 2,596 · see citing works
The Science of Stroke: Mechanisms in Search of Treatments
Moskowitz, M. A., Lo, E. H., & Iadecola, C. (2010) · Neuron · doi:10.1016/j.neuron.2010.07.002 · Cited by 1,930 · see citing works
Reactive Oxygen Radicals in Signaling and Damage in the Ischemic Brain
Chan, P. H. (2001) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200101000-00002 · Cited by 1,589 · see citing works
Inflammatory mechanisms in ischemic stroke: role of inflammatory cells
Jin, R., Yang, G., & Li, G. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.1109766 · Cited by 1,521 · see citing works
Update of the Stroke Therapy Academic Industry Roundtable Preclinical Recommendations
Fisher, M., Feuerstein, G., Howells, D. W., Hurn, P. D., Kent, T. A., Savitz, S. I., & Lo, E. H. (2009) · Stroke · doi:10.1161/strokeaha.108.541128 · Cited by 1,352 · see citing works
Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke
Gelderblom, M., Leypoldt, F., Steinbach, K., Behrens, D., Choe, C.-U., Siler, D. A., Arumugam, T. V., Orthey, E., Gerloff, C., Tolosa, E., et al. (2009) · Stroke · doi:10.1161/strokeaha.108.534503 · Cited by 1,066 · see citing works
(2001) · PubMed · Cited by 943 · see citing works
Intracellular pH transients in squid giant axons caused by CO2, NH3, and metabolic inhibitors.
Boron, W. F., & Weer, P. D. (1976) · The Journal of General Physiology · doi:10.1085/jgp.67.1.91 · Cited by 921 · see citing works
Selective Ablation of Proliferating Microglial Cells Exacerbates Ischemic Injury in the Brain
Lalancette-Hébert, M., Gowing, G., Simard, A., Weng, Y. C., & Kriz, J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5360-06.2007 · Cited by 874 · see citing works
Zhao, H., Kalivendi, S., Zhang, H., Joseph, J., Nithipatikom, K., Vásquez-Vivar, J., & Kalyanaraman, B. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00142-4 · Cited by 803 · see citing works
Voltage-Gated Proton Channels and Other Proton Transfer Pathways
DeCoursey, T. E. (2003) · Physiological Reviews · doi:10.1152/physrev.00028.2002 · Cited by 739 · see citing works
A voltage-gated proton-selective channel lacking the pore domain
Ramsey, I. S., Moran, M. M., Chong, J. A., & Clapham, D. E. (2006) · Nature · doi:10.1038/nature04700 · Cited by 612 · see citing works
Self-citationA Voltage Sensor-Domain Protein Is a Voltage-Gated Proton Channel
Sasaki, M., Takagi, M., & Okamura, Y. (2006) · Science · doi:10.1126/science.1122352 · Cited by 543 · see citing works
NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation
Brennan, A. M., Suh, S. W., Won, S. J., Narasimhan, P., Kauppinen, T. M., Lee, H., Edling, Y., Chan, P. H., & Swanson, R. A. (2009) · Nature Neuroscience · doi:10.1038/nn.2334 · Cited by 538 · see citing works
NOX Enzymes in the Central Nervous System: From Signaling to Disease
Sorce, S., & Krause, K. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2578 · Cited by 472 · see citing works
Kleinschnitz, C., Grund, H., Wingler, K., Armitage, M. E., Jones, E., Mittal, M., Barit, D., Schwarz, T., Geis, C., Kraft, P., et al. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000479 · Cited by 447 · see citing works
Why Have Antioxidants Failed in Clinical Trials?
Steinhubl, S. R. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.02.003 · Cited by 424 · see citing works
Hara, H., Huang, P. L., Panahian, N., Fishman, M. C., & Moskowitz, M. A. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199607000-00010 · Cited by 410 · see citing works
Boyarsky, G., Ganz, M. B., Sterzel, R. B., & Boron, W. F. (1988) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1988.255.6.c844 · Cited by 409 · see citing works
Microglial Activation in Stroke: Therapeutic Targets
Yenari, M. A., Kauppinen, T. M., & Swanson, R. A. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.07.005 · Cited by 390 · see citing works
Acid Extrusion from Human Spermatozoa Is Mediated by Flagellar Voltage-Gated Proton Channel
Lishko, P. V., Botchkina, I. L., Fedorenko, A., & Kirichok, Y. (2010) · Cell · doi:10.1016/j.cell.2009.12.053 · Cited by 387 · see citing works
Schilling, M., Besselmann, M., Leonhard, C., Mueller, M., Ringelstein, E. B., & Kiefer, R. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00082-7 · Cited by 375 · see citing works
Liu, R., Liu, I. Y., Bi, X., Thompson, R. F., Doctrow, S. R., Malfroy, B., & Baudry, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1332809100 · Cited by 365 · see citing works
Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase
Walder, C. E., Green, S. P., Darbonne, W. C., Mathias, J., Rae, J., Dinauer, M. C., Curnutte, J. T., & Thomas, G. R. (1997) · Stroke · doi:10.1161/01.str.28.11.2252 · Cited by 349 · see citing works
The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels
DeCoursey, T. E., Morgan, D., & Cherny, V. V. (2003) · Nature · doi:10.1038/nature01523 · Cited by 323 · see citing works
Hydrogen ion currents and intracellular pH in depolarized voltage-clamped snail neurones
THOMAS, R. C., & Meech, R. W. (1982) · Nature · doi:10.1038/299826a0 · Cited by 320 · see citing works
Kraft, R., Grimm, C. M., Grosse, K., Hoffmann, A., Sauerbruch, S., Kettenmann, H., Schultz, G., & Harteneck, C. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00331.2003 · Cited by 281 · see citing works
Oxidative and Antioxidative Potential of Brain Microglial Cells
Dringen, R. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.1223 · Cited by 266 · see citing works
Ramsey, I. S., Ruchti, E., Kaczmarek, J. S., & Clapham, D. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902761106 · Cited by 255 · see citing works
Self-citationSnapShot: Reactive Oxygen Intermediates (ROI)
Nathan, C., & Ding, A. H. (2010) · Cell · doi:10.1016/j.cell.2010.03.008 · Cited by 240 · see citing works
Capasso, M., Bhamrah, M. K., Henley, T., Boyd, R. S., Langlais, C., Cain, K., Dinsdale, D., Pulford, K., Khan, M., Musset, B., et al. (2010) · Nature Immunology · doi:10.1038/ni.1843 · Cited by 223 · see citing works
Lai, A. Y., & Todd, K. G. (2006) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y05-143 · Cited by 198 · see citing works
Wu, L., Vadakkan, K. I., & Zhuo, M. (2007) · Glia · doi:10.1002/glia.20500 · Cited by 156 · see citing works
Self-citationVoltage-gated proton channel is expressed on phagosomes
Okochi, Y., Sasaki, M., Iwasaki, H., & Okamura, Y. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.03.036 · Cited by 129 · see citing works
An in vitro model of ischemia: metabolic and electrical alterations in the hippocampal slice
Whittingham, T. S., Lust, W. D., & Passonneau, J. V. (1984) · Journal of Neuroscience · doi:10.1523/jneurosci.04-03-00793.1984 · Cited by 122 · see citing works
Microgliosis: the questions shape the answers
Ransohoff, R. M. (2007) · Nature Neuroscience · doi:10.1038/nn1207-1507 · Cited by 109 · see citing works
Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T
Iovannisci, D. M., Illek, B., & Fischer, H. (2010) · The Journal of General Physiology · doi:10.1085/jgp.200910379 · Cited by 88 · see citing works
A pH-stabilizing role of voltage-gated proton channels in IgE-mediated activation of human basophils
Musset, B., Morgan, D., Cherny, V. V., MacGlashan, D. W., Thomas, L. L., Rı́os, E., & DeCoursey, T. E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800886105 · Cited by 82 · see citing works
Resting Microglial Motility Is Independent of Synaptic Plasticity in Mammalian Brain
Wu, L., & Zhuo, M. (2008) · Journal of Neurophysiology · doi:10.1152/jn.01210.2007 · Cited by 81 · see citing works
Self-citationLyons, S. A., Pastor, A., Ohlemeyer, C., Kann, O., Wiegand, F., Prass, K., Knapp, F., Kettenmann, H., & Dirnagl, U. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200011000-00003 · Cited by 72 · see citing works
Ion channels in rat microglia and their different sensitivity to lipopolysaccharide and interferon‐γ
Visentin, S., Agresti, C., Patrizio, M., & Levi, G. (1995) · Journal of Neuroscience Research · doi:10.1002/jnr.490420402 · Cited by 70 · see citing works
Ion channel expression in resting and activated microglia of hippocampal slices from juvenile mice
Schilling, T., & Eder, C. (2007) · Brain Research · doi:10.1016/j.brainres.2007.10.027 · Cited by 66 · see citing works
Voltage‐gated proton channels: what's next?
DeCoursey, T. E. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.161703 · Cited by 58 · see citing works
Simoni, A. D., Allen, N. J., & Attwell, D. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06417.x · Cited by 27 · see citing works
Cheng, Y. M., Kelly, T., & Church, J. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.12.007 · Cited by 26 · see citing works
Flagged first, then by citations
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Ion Channels in Innate and Adaptive Immunity
Feske, S., Wulff, H., & Skolnik, E. Y. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112212 · Cited by 764 · see citing works
Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links.
Oguntibeju, O. O. (2019) · Europe PMC (PubMed Central) · Cited by 758 · see citing works
The biphasic function of microglia in ischemic stroke
Ma, Y., Wang, J., Wang, Y., & Yang, G. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.01.005 · Cited by 724 · see citing works
Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes
Nortley, R., Korte, N., Izquierdo, P., Hirunpattarasilp, C., Mishra, A., Jaunmuktane, Z., Kyrargyri, V., Pfeiffer, T., Khennouf, L., Madry, C., et al. (2019) · Science · doi:10.1126/science.aav9518 · Cited by 682 · see citing works
Oxidative Stress in Type 2 Diabetes: Impacts from Pathogenesis to Lifestyle Modifications
Caturano, A., D’Angelo, M., Mormone, A., Russo, V., Mollica, M. P., Salvatore, T., Galiero, R., Rinaldi, L., Vetrano, E., Marfella, R., et al. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45080420 · Cited by 579 · see citing works
Dual Functions of Microglia in Ischemic Stroke
Qin, C., Zhou, L., Ma, X.-T., Hu, Z.-W., Yang, S., Chen, M., Bosco, D. B., Wu, L., & Tian, D. (2019) · Neuroscience Bulletin · doi:10.1007/s12264-019-00388-3 · Cited by 546 · see citing works
Self-citationEyo, U. B., Peng, J., Swiatkowski, P., Mukherjee, A., Bispo, A., & Wu, L.-J. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0416-14.2014 · Cited by 509 · see citing works
Self-citationFunctions and dysfunctions of nitric oxide in brain
Picón-Pagès, P., Garcia-Buendia, J., & Muñoz, F. J. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.11.007 · Cited by 357 · see citing works
Modulators of microglia activation and polarization in ischemic stroke
Jiang, C., Wu, W., Deng, Y.-H., & Ge, J.-W. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11003 · Cited by 355 · see citing works
Microglia–Neuron Communication in Epilepsy
Eyo, U. B., Murugan, M., & Wu, L. (2016) · Glia · doi:10.1002/glia.23006 · Cited by 290 · see citing works
Self-citationNew Insights on <i>NOX</i> Enzymes in the Central Nervous System
Nayernia, Z., Jaquet, V., & Krause, K.-H. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5703 · Cited by 279 · see citing works
Li, P., Stetler, R. A., Leak, R. K., Shi, Y., Li, Y., Yu, W., Bennett, M. V. L., & Chen, J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.011 · Cited by 260 · see citing works
Voltage-Gated Proton Channels: Molecular Biology, Physiology, and Pathophysiology of the HVFamily
DeCoursey, T. E. (2013) · Physiological Reviews · doi:10.1152/physrev.00011.2012 · Cited by 221 · see citing works
X-ray crystal structure of voltage-gated proton channel
Takeshita, K., Sakata, S., Yamashita, E., Fujiwara, Y., Kawanabe, A., Kurokawa, T., Okochi, Y., Matsuda, M., Narita, H., Okamura, Y., et al. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2783 · Cited by 209 · see citing works
Li, M., Li, Z., Yao, Y., Jin, W., Wood, K., Liu, Q., Shi, F., & Hao, J. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612930114 · Cited by 206 · see citing works
Tian, D., Peng, J., Murugan, M., Feng, L.-J., Liu, J., Eyo, U. B., Zhou, L., Mogilevsky, R., Wang, W., & Wu, L. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0315-17.2017 · Cited by 201 · see citing works
Self-citationCognitive Deficits and Delayed Neuronal Loss in a Mouse Model of Multiple Microinfarcts
Wang, M., Iliff, J. J., Liao, Y., Chen, M. J., Shinseki, M. S., Venkataraman, A., Cheung, J., Wang, W., & Nedergaard, M. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1860-12.2012 · Cited by 183 · see citing works
Zeng, J., Bao, T., Yang, K., Zhu, X., Wang, S., Xiang, W., Ge, A., Zeng, L., & Ge, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1047550 · Cited by 175 · see citing works
Modulation of Microglial Process Convergence Toward Neuronal Dendrites by Extracellular Calcium
Eyo, U. B., Gu, N., De, S., Dong, H., Richardson, J. R., & Wu, L.-J. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3279-14.2015 · Cited by 154 · see citing works
Self-citationChen, S., Shao, L., & Ma, L. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.716825 · Cited by 150 · see citing works
Microglia: Key Elements in Neural Development, Plasticity, and Pathology
Eyo, U. B., & Dailey, M. E. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9434-z · Cited by 138 · see citing works
Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain
Gu, N., Eyo, U. B., Murugan, M., Peng, J., Matta, S., Dong, H., & Wu, L. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.11.007 · Cited by 131 · see citing works
Self-citationMicroglial TLR4-dependent autophagy induces ischemic white matter damage via STAT1/6 pathway
Qin, C., Liu, Q., Hu, Z.-W., Zhou, L., Shang, K., Bosco, D. B., Wu, L., Tian, D., & Wang, W. (2018) · Theranostics · doi:10.7150/thno.27882 · Cited by 131 · see citing works
Self-citationTuning neural circuits and behaviors by microglia in the adult brain
Zhao, S., Umpierre, A. D., & Wu, L. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2023.12.003 · Cited by 116 · see citing works
Self-citationMicroglial interactions with the neurovascular system in physiology and pathology
Zhao, X., Eyo, U. B., Murugan, M., & Wu, L. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22576 · Cited by 109 · see citing works
Self-citationMicroglial CMPK2 promotes neuroinflammation and brain injury after ischemic stroke
Guan, X., Zhu, S., Song, J.-Q., Liu, K., Liu, M., Xie, L., Wang, Y., Wu, J. S., Xu, X., & Pang, T. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101522 · Cited by 111 · see citing works
ROS: Executioner of regulating cell death in spinal cord injury
Yin, Z., Wan, B., Gong, G., & Yin, J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1330678 · Cited by 106 · see citing works
Ion Channels and Receptors as Determinants of Microglial Function
Izquierdo, P., Attwell, D., & Madry, C. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2018.12.007 · Cited by 102 · see citing works
Zong, P., Feng, J., Yue, Z., Li, Y., Wu, G., Sun, B., He, Y., Miller, B. A., Yu, A. S., Su, Z., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.03.021 · Cited by 102 · see citing works
Self-citationFeng, L., Murugan, M., Bosco, D. B., Liu, Y., Peng, J., Worrell, G. A., Wang, H., Ta, L. E., Richardson, J. R., Shen, Y., et al. (2019) · Glia · doi:10.1002/glia.23616 · Cited by 96 · see citing works
Self-citationMolecular determinants of Hv1 proton channel inhibition by guanidine derivatives
Hong, L., Kim, I. H., & Tombola, F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1324012111 · Cited by 99 · see citing works
Focusing on mitochondria in the brain: from biology to therapeutics
Song, N., Mei, S., Wang, X.-X., Hu, G., & Lu, M. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00409-w · Cited by 102 · see citing works
Hong, L., Pathak, M. M., Kim, I. H., Ta, D. T., & Tombola, F. (2013) · Neuron · doi:10.1016/j.neuron.2012.11.013 · Cited by 94 · see citing works
Ion Channels in Neurological Disorders
Kumar, P., Kumar, D., Jha, S. K., Jha, N. K., & Ambasta, R. K. (2015) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2015.10.006 · Cited by 90 · see citing works
Voltage and pH sensing by the voltage-gated proton channel, HV1
DeCoursey, T. E. (2018) · Journal of The Royal Society Interface · doi:10.1098/rsif.2018.0108 · Cited by 88 · see citing works
Zhao, S., Yin, J., Zhou, L., Yan, F., He, Q., Li, H., Peng, S., Jia, J., Cheng, J., Chen, H., et al. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.12.016 · Cited by 86 · see citing works
Li, X., Yu, Z., Zong, W., Chen, P., Li, J., Wang, M., Ding, F., Xie, M., Wang, W. T., & Luo, X. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01942-x · Cited by 86 · see citing works
Ritzel, R. M., He, J., Li, Y., Cao, T., Khan, N., Shim, B., Sabirzhanov, B. E., Aubrecht, T. G., Stoica, B. A., Faden, A. I., et al. (2020) · Glia · doi:10.1002/glia.23926 · Cited by 83 · see citing works
Self-citationTian, D., Li, C., Qin, C., Murugan, M., Wu, L., & Liu, J. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13751 · Cited by 84 · see citing works
Self-citationHydrophobic plug functions as a gate in voltage-gated proton channels
Chamberlin, A. C., Qiu, F., Rebolledo, S., Wang, Y., Noskov, S. Y., & Larsson, H. P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318018111 · Cited by 82 · see citing works
Ion channels and transporters in microglial function in physiology and brain diseases
Luo, L., Song, S., Ezenwukwa, C. C., Jalali, S., Sun, B., & Sun, D. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104925 · Cited by 79 · see citing works
Li, M., Zhou, Z., Sun, M., Cao, L., Chen, J., Qin, Y., Gu, J., Han, F., Sheng, R., Wu, J., et al. (2015) · Stroke · doi:10.1161/strokeaha.115.009687 · Cited by 77 · see citing works
Construction and validation of a homology model of the human voltage-gated proton channel hHV1
Kulleperuma, K., Smith, S. M., Morgan, D., Musset, B., Holyoake, J., Chakrabarti, N., Cherny, V. V., DeCoursey, T. E., & Pomès, R. (2013) · The Journal of General Physiology · doi:10.1085/jgp.201210856 · Cited by 76 · see citing works
Optogenetic activation of spinal microglia triggers chronic pain in mice
Yi, M., Liu, Y., Umpierre, A. D., Chen, T., Ying, Y., Zheng, J., Dheer, A., Bosco, D. B., Dong, H., & Wu, L. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3001154 · Cited by 75 · see citing works
Self-citationP2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation
Eyo, U. B., Miner, S. A., Ahlers‐Dannen, K. E., Wu, L., & Dailey, M. E. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.032 · Cited by 75 · see citing works
Self-citationMortadza, S. A. S., Sim, J. A., Stacey, M. A., & Jiang, L. (2017) · Scientific Reports · doi:10.1038/srep45032 · Cited by 74 · see citing works
Li, T., Zhao, J., Xie, W., Yuan, W., Guo, J., Pang, S., Gan, W.-B., Gómez-Nicola, D., & Zhang, S. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02127-w · Cited by 72 · see citing works
Zhang, Q., Ren, Y., Mo, Y., Guo, P., Liao, P. S., Luo, Y., Mu, J., Chen, Z., Zhang, Y., Li, Y., et al. (2022) · Cell Research · doi:10.1038/s41422-022-00616-y · Cited by 72 · see citing works
Voltage-Gated Proton Channels as Novel Drug Targets: From NADPH Oxidase Regulation to Sperm Biology
Seredenina, T. S., Demaurex, N., & Krause, K. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5806 · Cited by 72 · see citing works
Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production
Spencer, N. G., Schilling, T., Miralles, F., & Eder, C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162497 · Cited by 72 · see citing works
Subunit Interactions during Cooperative Opening of Voltage-Gated Proton Channels
Qiu, F., Rebolledo, S., Gonzalez, C. L., & Larsson, H. P. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.021 · Cited by 69 · see citing works
Microglial Hv1 proton channel promotes cuprizone-induced demyelination through oxidative damage
Liu, J.-L., Tian, D.-S., Murugan, M., Eyo, U. B., Dreyfus, C. F., Wang, W., & Wu, L.-J. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13242 · Cited by 67 · see citing works
Self-citationLi, Y., Ritzel, R. M., He, J., Cao, T., Sabirzhanov, B. E., Li, H., Liu, S., Wu, L., & Wu, J. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.10.005 · Cited by 67 · see citing works
Self-citationPhilosophy of voltage-gated proton channels
DeCoursey, T. E., & Hosler, J. P. (2013) · Journal of The Royal Society Interface · doi:10.1098/rsif.2013.0799 · Cited by 67 · see citing works
Li, Z., Fang, F., Wang, Y., & Wang, L. (2016) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2016.04.007 · Cited by 64 · see citing works
Selectivity Mechanism of the Voltage-gated Proton Channel, HV1
Dudev, T., Musset, B., Morgan, D., Cherny, V. V., Smith, S. M. E., Mazmanian, K., DeCoursey, T. E., & Lim, C. (2015) · Scientific Reports · doi:10.1038/srep10320 · Cited by 60 · see citing works
Molecular mechanism of Zn 2+ inhibition of a voltage-gated proton channel
Qiu, F., Chamberlin, A. C., Watkins, B. M., Ionescu, A., Perez, M. E., Barro-Soria, R., Gonzalez, C. L., Noskov, S. Y., & Larsson, H. P. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1604082113 · Cited by 60 · see citing works
Nicotinic Acetylcholine Receptor Signaling in Neuroprotection
Akaike, A., Shimohama, S., & Misu, Y. (2018) · Springer eBooks · doi:10.1007/978-981-10-8488-1 · Cited by 60 · see citing works
Microglial Responses to Brain Injury and Disease: Functional Diversity and New Opportunities
Lyu, J., Jiang, X., Leak, R. K., Shi, Y., Hu, X., & Chen, J. (2020) · Translational Stroke Research · doi:10.1007/s12975-020-00857-2 · Cited by 61 · see citing works
Han, Y., Xu, Z., Qu, G., Wang, H., Lin, L., Li, X., Xie, X., Lei, Y., He, X., Chen, Y., et al. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00868-5 · Cited by 57 · see citing works
Fan, H., Bai, Q., Yang, Y., Shi, X., Du, G., Yan, J., Shi, J., & Wang, D. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175966 · Cited by 57 · see citing works
A specialized molecular motion opens the Hv1 voltage-gated proton channel
Mony, L., Berger, T. K., & Isacoff, E. Y. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2978 · Cited by 55 · see citing works
NADPH Oxidase-2: Linking Glucose, Acidosis, and Excitotoxicity in Stroke
Brennan, A., Won, S. J., & Swanson, R. A. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5767 · Cited by 53 · see citing works
DeCoursey, T. E. (2016) · Immunological Reviews · doi:10.1111/imr.12437 · Cited by 54 · see citing works
Post‐translational cleavage of Hv1 in human sperm tunes pH‐ and voltage‐dependent gating
Berger, T. K., Fußhöller, D. M., Goodwin, N., Bönigk, W., Müller, A., Khesroshahi, N. D., Brenker, C., Wachten, D., Krause, E., Kaupp, U. B., et al. (2016) · The Journal of Physiology · doi:10.1113/jp273189 · Cited by 53 · see citing works
Zhang, Z., Zheng, X., Zhang, X., Zhang, Y., Huang, B., & Luo, T. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13271 · Cited by 52 · see citing works
Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain
Parusel, S., Yi, M., Hunt, C., & Wu, L. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00937-3 · Cited by 51 · see citing works
Self-citationZhao, R., Dai, H., Arias, R., Blas, G. A. D., Orta, G., Pavarotti, M. A., Shen, R., Perozo, E., Mayorga, L. S., Darszon, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24145-1 · Cited by 51 · see citing works
Voltage-Gated Proton Channel H V 1 in Microglia
Wu, L. (2014) · The Neuroscientist · doi:10.1177/1073858413519864 · Cited by 49 · see citing works
Self-citationHou, K., Li, G., Yu, J., Xu, K., & Wu, W. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2021.02.018 · Cited by 49 · see citing works
Microglial Hv1 proton channels promote white matter injuries after chronic hypoperfusion in mice
Yu, Y., Luo, X., Li, C., Ding, F., Wang, M., Xie, M., Yu, Z., Ransom, B. R., & Wang, W. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14925 · Cited by 47 · see citing works
Wu, Y., Yao, J., & Feng, K. (2020) · Neurochemical Research · doi:10.1007/s11064-019-02931-0 · Cited by 48 · see citing works
The Voltage-Gated Proton Channel: A Riddle, Wrapped in a Mystery, inside an Enigma
DeCoursey, T. E. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00353 · Cited by 48 · see citing works
The volume-regulated anion channel (LRRC8) in nodose neurons is sensitive to acidic pH
Wang, R., Lu, Y., Gunasekar, S. K., Zhang, Y., Benson, C. J., Chapleau, M. W., Sah, R., & Abboud, F. M. (2017) · JCI Insight · doi:10.1172/jci.insight.90632 · Cited by 47 · see citing works
Chen, M., Yang, L.-L., Hu, Z.-W., Qin, C., Zhou, L., Duan, Y.-L., Bosco, D. B., Wu, L., Zhan, K., Xu, S.-B., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02020-y · Cited by 47 · see citing works
Self-citationHv1 Proton Channel Opening Is Preceded by a Voltage-independent Transition
Villalba‐Galea, C. A. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.08.017 · Cited by 46 · see citing works
Microglial Voltage-Gated Proton Channel Hv1 in Ischemic Stroke
Wu, L. (2013) · Translational Stroke Research · doi:10.1007/s12975-013-0289-7 · Cited by 46 · see citing works
Self-citationMicroglia: A Unique Versatile Cell in the Central Nervous System
Masuda, T., & Prinz, M. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00317 · Cited by 45 · see citing works
Tryptophan 207 is crucial to the unique properties of the human voltage-gated proton channel, hHV1
Cherny, V. V., Morgan, D., Musset, B., Chaves, G., Smith, S. M. E., & DeCoursey, T. E. (2015) · The Journal of General Physiology · doi:10.1085/jgp.201511456 · Cited by 45 · see citing works
Gating Mechanisms of Voltage-Gated Proton Channels
Okamura, Y., Fujiwara, Y., & Sakata, S. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034307 · Cited by 45 · see citing works
Transient Receptor Potential Channels in Microglia: Roles in Physiology and Disease
Echeverry, S., Rodríguez, M. J., & Torres, Y. P. (2016) · Neurotoxicity Research · doi:10.1007/s12640-016-9632-6 · Cited by 45 · see citing works
Eyo, U. B., & Dailey, M. E. (2012) · Glia · doi:10.1002/glia.22394 · Cited by 44 · see citing works
Bierbower, S. M., Choveau, F. S., Lechleiter, J. D., & Shapiro, M. S. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3805-14.2015 · Cited by 45 · see citing works
Nazari, Q. A., Kume, T., Takada‐Takatori, Y., Izumi, Y., & Akaike, A. (2013) · Journal of Pharmacological Sciences · doi:10.1254/jphs.13019fp · Cited by 43 · see citing works
Morgan, D., Musset, B., Kulleperuma, K., Smith, S. M. E., Rajan, S., Cherny, V. V., Pomès, R., & DeCoursey, T. E. (2013) · The Journal of General Physiology · doi:10.1085/jgp.201311045 · Cited by 42 · see citing works
Effects of metabolic acidosis on intracellular pH responses in multiple cell types
Salameh, A., Ruffin, V. A., & Boron, W. F. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00154.2014 · Cited by 41 · see citing works
Peng, J., Yi, M., Jeong, H., McEwan, S. A., Zheng, J., Wu, G., Ganatra, S., Ren, Y., Richardson, J. R., Oh, S. B., et al. (2021) · Molecular Brain · doi:10.1186/s13041-021-00812-8 · Cited by 41 · see citing works
Self-citationAutoimmune disorder phenotypes in Hvcn1-deficient mice.
Sasaki, M., Tojo, A., Okochi, Y., Miyawaki, N., Kamimura, D., Yamaguchi, A., Murakami, M., & Okamura, Y. (2013) · Biochemical Journal · doi:10.1042/bj20121188 · Cited by 41 · see citing works
Noda, M., & Kobayashi, A. (2016) · The Journal of Physiological Sciences · doi:10.1007/s12576-016-0460-5 · Cited by 40 · see citing works
Mib2 Deficiency Inhibits Microglial Activation and Alleviates Ischemia-Induced Brain Injury
Li, X., Liao, Y., Dong, Y., Li, S., Wang, F., Wu, R., Yuan, Z., & Cheng, J. (2020) · Aging and Disease · doi:10.14336/ad.2019.0807 · Cited by 39 · see citing works
Zeng, W.-Z., Liu, D.-S., Liu, L., She, L., Wu, L., & Xu, T. (2015) · Scientific Reports · doi:10.1038/srep14125 · Cited by 40 · see citing works
Self-citationThe Hv1 proton channel responds to mechanical stimuli
Pathak, M. M., Tran, T. T., Hong, L., Joós, B., Morris, C. E., & Tombola, F. (2016) · The Journal of General Physiology · doi:10.1085/jgp.201611672 · Cited by 38 · see citing works
On the role of water density fluctuations in the inhibition of a proton channel
Gianti, E., Delemotte, L., Klein, M. L., & Carnevale, V. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1609964114 · Cited by 38 · see citing works
Geragotelis, A. D., Wood, M. L., Göddeke, H., Hong, L., Webster, P. D., Wong, E. K., Freites, J. A., Tombola, F., & Tobias, D. J. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920943117 · Cited by 38 · see citing works
Promising targets of cell death signaling of NR2B receptor subunit in stroke pathogenesis
Shu, S., Pei, L., & Lu, Y. (2014) · Regenerative Medicine Research · doi:10.1186/2050-490x-2-8 · Cited by 37 · see citing works
van Keulen, S. C., Gianti, E., Carnevale, V., Klein, M. L., Röthlisberger, U., & Delemotte, L. (2016) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6b08339 · Cited by 37 · see citing works
Yu, Y., Yu, Z., Xie, M., Wang, W., & Luo, X. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.06.197 · Cited by 37 · see citing works
Qian, C., Li, P., Jiao, Y., Yao, H., Chen, Y., Yang, J. Z., Ding, J., Yang, X., & Teng, G. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153756 · Cited by 36 · see citing works
Microglia in Alzheimer's Disease: A Role for Ion Channels
Thei, L., Imm, J. L., Kaisis, E., Dallas, M. L., & Kerrigan, T. L. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00676 · Cited by 37 · see citing works
Liu, S., Gao, Y., Yu, X., Zhao, B., Liu, L., Zhao, Y., Luo, Z., & Shi, J. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101770 · Cited by 36 · see citing works
- Authors
- Wu, L.-J., Wu, G., Sharif, M. R. A., Baker, A., Jia, Y., Fahey, F. H., Luo, H. R., Feener, E. P., & Clapham, D. E.
- Affiliations
- Boston Children's Hospital (US)
- Joslin Diabetes Center (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Clapham, David E
- Venue
- Nature Neuroscience
- Published
- 2012-03-04
- Volume
- 15
- Issue
- 4
- Pages
- 565-573
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3314139
- OpenAlex
- W2166577272
- Cited by
- 252
- References
- 50
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 17 · 2023: 20 · 2022: 13 · 2021: 20 · 2020: 27 · 2019: 11 · 2018: 9 · 2017: 12 · 2016: 26 · 2015: 19 · 2014: 20 · 2013: 22 · 2012: 6
- FWCI
- 10.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (R01MH090293)
- National Eye Institute (R01EY019029)
- National Institute of General Medical Sciences (R01GM076084)
- National Institute of Neurological Disorders and Stroke (P01NS072040)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- ischemic stroke, NADPH oxidase, reactive oxygen species, microglia, neuronal cell death, brain damage, innate immunity, proton current, therapeutic target
- MeSH terms
- Animals, Brain, Cells, Cultured, Brain Ischemia, Humans, Ion Channels, Mice, Inbred C57BL, Mice, Transgenic, Organ Culture Techniques, Random Allocation, Rats, Sprague-Dawley, Reactive Oxygen Species, Mice, Knockout, Stroke, Mice, Rats
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