The Two-Pore-Domain K+ Channels TREK-1 and TASK-3 Are Differentially Modulated by Copper and Zinc

Gruss, M., Mathie, A., Lieb, W.R. and Franks, N.P. 2004. The Two-Pore-Domain K+ Channels TREK-1 and TASK-3 Are Differentially Modulated by Copper and Zinc. Molecular Pharmacology. 66 (3), pp. 530-537.

TitleThe Two-Pore-Domain K+ Channels TREK-1 and TASK-3 Are Differentially Modulated by Copper and Zinc
TypeJournal article
AuthorsGruss, M., Mathie, A., Lieb, W.R. and Franks, N.P.
Abstract

The “trace” elements copper and zinc are essential for life, and their role in the function of metalloproteins is well known. However, mounting evidence shows that these metals are also capable of modulating neuronal excitability under normal physiological conditions. They are present at high levels in the brain, are concentrated at nerve terminals, and are released at micromolar concentrations into the synaptic cleft after depolarization. They have been shown to affect the function of a number of different voltage- and ligand-gated ion channels, but their most important targets in the nervous system remain uncertain. In this study, we show that the two-pore-domain potassium channels TREK-1 and TASK-3 are potently modulated by both copper and zinc. Copper activates TREK-1 channels by 83 ± 11% with an EC50 of 3.0 ± 1.0 μM, whereas TASK-3 channels are potently inhibited, with an IC50 of 2.7 ± 0.4 μM. Zinc inhibits both channels but with very different affinities. The IC50 for inhibition of TREK-1 channels is 659 ± 94 μM whereas the IC50 for inhibition of TASK-3 is 12.7 ± 1.0 μM. Using site-directed mutagenesis, we show that Asp128 plays a critical role in the copper activation of TREK-1. These observations provide a novel explanation for how copper and zinc might affect neuronal excitability under both normal physiological conditions, as well as during diseases in which copper or zinc homeostasis has been disrupted.

JournalMolecular Pharmacology
Journal citation66 (3), pp. 530-537
ISSN0026-895X
Year2004
PublisherAmerican Society for Pharmacology and Experimental Therapeutics
PubMed ID15322244
Web address (URL)https://molpharm.aspetjournals.org/content/66/3/530
Publication dates
Published01 Sep 2004

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Savickas, Vilius, Stewart, Adrian J., Rees-Roberts, Melanie, Short, Vanessa, Bhamra, Sukvinder K., Corlett, Sarah A., Mathie, A. and Veale, Emma L. 2020. Opportunistic screening for atrial fibrillation by clinical pharmacists in UK general practice during the influenza vaccination season: A cross-sectional feasibility study. PLoS Medicine. 17 (7) e1003197. https://doi.org/10.1371/journal.pmed.1003197

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters
Stephen P.H. Alexander, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Joanna L. Sharman, Christopher Southan and Jamie A. Davies 2019. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology. 176 (S1), pp. S397-S493. https://doi.org/10.1111/bph.14753

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Enzymes
Stephen P.H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Joanna L. Sharman, Christopher Southan and Jamie A. Davies 2019. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Enzymes. British Journal of Pharmacology. 176 (S1), pp. S297-S396. https://doi.org/10.1111/bph.14752

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein‐coupled receptors
Stephen P.H. Alexander, Arthur Christopoulos, Anthony P. Davenport, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Joanna L. Sharman, Christopher Southan and Jamie A. Davies 2019. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein‐coupled receptors. British Journal of Pharmacology. 176 (S1), pp. S21-S141. https://doi.org/10.1111/bph.14748

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Introduction and Other Protein Targets
Stephen P.H. Alexander, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Joanna L. Sharman, Christopher Southan, O. Peter Buneman, John A. Cidlowski, Arthur Christopoulos, Anthony P. Davenport, Doriano Fabbro, Michael Spedding, Jörg Striessnig and Jamie A. Davies 2019. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Introduction and Other Protein Targets. British Journal of Pharmacology. 176, pp. S1-S20. https://doi.org/10.1111/bph.14747

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Nuclear hormone receptors
Stephen P H Alexander, John A Cidlowski, Eamonn Kelly, Alistair Mathie, John A Peters, Emma L Veale, Jane F Armstrong, Elena Faccenda, Simon D Harding, Adam J Pawson, Joanna L Sharman, Christopher Southan and Jamie A Davies 2019. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Nuclear hormone receptors. British Journal of Pharmacology. https://doi.org/10.1111/bph.14750

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Catalytic receptors
Stephen P.H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Joanna L. Sharman, Christopher Southan and Jamie A. Davies 2019. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Catalytic receptors. British Journal of Pharmacology. 176, pp. S247-S296. https://doi.org/10.1111/bph.14751

The Concise Guide to Pharmacology 2019/20: Ion channels
Stephen P.H. Alexander, Alistair Mathie, John A. Peters, Emma L. Veale, Jörg Striessnig, Eamonn Kelly, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Joanna L. Sharman, Christopher Southan and Jamie A. Davies 2019. The Concise Guide to Pharmacology 2019/20: Ion channels. British Journal of Pharmacology. 176 (S1), pp. S142-S228. https://doi.org/10.1111/bph.14749

Pranlukast is a novel small molecule activator of the two-pore domain potassium channel TREK2
Wright, P.D., McCoull, D., Walsh, Y., Large, J.M., Hadrys, B.W., Gaurilcikaite, E., Byrom, L., Veale, E.L., Jerman, J. and Mathie, A. 2019. Pranlukast is a novel small molecule activator of the two-pore domain potassium channel TREK2. Biochemical and Biophysical Research Communications. 520 (1), pp. 35-40. https://doi.org/10.1016/j.bbrc.2019.09.093

Editorial: Infection in pulmonary vascular diseases: Would another consortium really be the way to go?
Butrous, G. and Mathie, A. 2019. Editorial: Infection in pulmonary vascular diseases: Would another consortium really be the way to go? Global Cardiology Science & Practice. 2019 (1). https://doi.org/10.21542/gcsp.2019.1

Pharmacologically reversible, loss of function mutations in the TM2 and TM4 inner pore helices of TREK-1 K2P channels
Ehab Al-Moubarak, Emma L. Veale and Alistair Mathie 2019. Pharmacologically reversible, loss of function mutations in the TM2 and TM4 inner pore helices of TREK-1 K2P channels. Scientific Reports. 9 12394. https://doi.org/10.1038/s41598-019-48855-1

Characterization and regulation of wild‐type and mutant TASK‐1 two pore domain potassium channels indicated in pulmonary arterial hypertension
Cunningham, K.P., Holden, R.G., Escribano‐Subias, P.M., Cogolludo, A., Veale, E.L. and Mathie, A. 2019. Characterization and regulation of wild‐type and mutant TASK‐1 two pore domain potassium channels indicated in pulmonary arterial hypertension. Journal of Physiology. 597 (4), pp. 1087-1101. https://doi.org/10.1113/jp277275

GI-530159, a novel, selective, mechano-sensitive K2P channel opener, reduces rat dorsal root ganglion (DRG) neuron excitability
Alexandre J.C. Loucif, Pierre-Philippe Saintot, Jia Liu, Brett M. Antonio, Shannon G. Zellmer, Katrina Yoger, Emma L. Veale, Anna Wilbrey, Kiyoyuki Omoto, Lishuang Cao, Alex Gutteridge, Neil A. Castle, Edward B. Stevens and Alistair Mathie 2018. GI-530159, a novel, selective, mechano-sensitive K2P channel opener, reduces rat dorsal root ganglion (DRG) neuron excitability. British Journal of Pharmacology. 175 (12), pp. 2272-2283. https://doi.org/10.1111/bph.14098

HIV transgene expression impairs K+ channel function in the pulmonary vasculature
Mondejar-Parreño, G., Morales-Cano, D., Barreira, B., Callejo, M., Ruiz-Cabello, J., Moreno, L., Esquivel-Ruiz, S., Mathie, A., Butrous, G., Perez-Vizcaino, F. and Cogolludo, A. 2018. HIV transgene expression impairs K+ channel function in the pulmonary vasculature. American Journal of Physiology: Lung and Molecular Physiology. 315 (5), pp. L711-L723. https://doi.org/10.1152/ajplung.00045.2018

Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons.
Fernández-Fernández, D., Cadaveira-Mosquera, A., Rueda-Ruzafa, L., Herrera-Pérez, S., Veale, E.L., Reboreda, A., Mathie, A. and Lamas, J.A. 2018. Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons. PLoS ONE. 13 (6) e0199282. https://doi.org/10.1371/journal.pone.0199282

Pharmacists detecting atrial fibrillation (PDAF) in primary care during the influenza vaccination season: a multisite, cross-sectional screening protocol
Emma L Veale, Adrian J Stewart, Alistair Mathie, Satvinder K Lall, Melanie Rees-Roberts, Vilius Savickas, Sukvinder K Bhamra and Sarah A Corlett 2018. Pharmacists detecting atrial fibrillation (PDAF) in primary care during the influenza vaccination season: a multisite, cross-sectional screening protocol. BMJ Open. 8 (3) e021121. https://doi.org/10.1136/bmjopen-2017-021121

Terbinafine is a novel and selective activator of the two-pore domain potassium channel TASK3
Paul D. Wright, Emma L. Veale, David McCoull, David C. Tickle, Jonathan M. Large, Emma Ococks, Gemma Gothard, Catherine Kettleborough, Alistair Mathie and Jeffrey Jerman 2017. Terbinafine is a novel and selective activator of the two-pore domain potassium channel TASK3. Biochemical and Biophysical Research Communications. 493 (1), pp. 444-450. https://doi.org/10.1016/j.bbrc.2017.09.002

Enhanced inflammatory cell profiles in schistosomiasis-induced pulmonary vascular remodeling
Ali, Z., Kosanovic, D., Kolosionek, E., Schermuly, R.T., Graham, B.B., Mathie, A. and Butrous, G. 2017. Enhanced inflammatory cell profiles in schistosomiasis-induced pulmonary vascular remodeling. Pulmonary Circulation. 7 (1), pp. 244-252. https://doi.org/10.1086/690687

TASK-1 (KCNK3) channels in the lung: from cell biology to clinical implications
Andrea Olschewski, Emma L. Veale, Bence M. Nagy, Chandran Nagaraj, Grazyna Kwapiszewska, Fabrice Antigny, Mélanie Lambert, Marc Humbert, Gábor Czirják, Péter Enyedi and Alistair Mathie 2017. TASK-1 (KCNK3) channels in the lung: from cell biology to clinical implications. The European Respiratory Journal. 50 (5) 1700754. https://doi.org/10.1183/13993003.00754-2017

Aristolochic acid, a plant extract used in the treatment of pain and linked to Balkan Endemic Nephropathy, is a regulator of K2P channels
Veale, E.L. and Mathie, A. 2016. Aristolochic acid, a plant extract used in the treatment of pain and linked to Balkan Endemic Nephropathy, is a regulator of K2P channels. British Journal of Pharmacology. 173 (10), pp. 1639-1652. https://doi.org/10.1111/bph.13465

Two-pore domain potassium channels: Potential therapeutic targets for the treatment of pain
Mathie, A. and Veale, E.L. 2015. Two-pore domain potassium channels: Potential therapeutic targets for the treatment of pain. Pflügers Archiv - European Journal of Physiology. 467, pp. 931-943. https://doi.org/10.1007/s00424-014-1655-3

Influence of the N terminus on the biophysical properties and pharmacology of TREK1 potassium channels
Veale, E.L., Al-Moubarak, E., Bajaria, N., Omoto, K., Cao, L., Tucker, S.J., Stevens, E.B. and Mathie, A. 2014. Influence of the N terminus on the biophysical properties and pharmacology of TREK1 potassium channels. Molecular Pharmacology. 85 (5), pp. 671-681. https://doi.org/10.1124/mol.113.091199

Enhancement of TWIK-related acid-sensitive potassium channel 3 (TASK3) two-pore domain potassium channel activity by tumor necrosis factor α
El Hachmane, M.F., Rees, K.A., Veale, E.L., Sumbayev, V.V. and Mathie, A. 2014. Enhancement of TWIK-related acid-sensitive potassium channel 3 (TASK3) two-pore domain potassium channel activity by tumor necrosis factor α. Journal of Biological Chemistry. 289 (3), pp. P1388-1401. https://doi.org/10.1074/jbc.m113.500033

Recovery of current through mutated TASK3 potassium channels underlying birk barel syndrome
Veale, E.L., Hassan, M., Walsh, Y., Al-Moubarak, E. and Mathie, A. 2014. Recovery of current through mutated TASK3 potassium channels underlying birk barel syndrome. Molecular Pharmacology. 85 (3), pp. 397-407. https://doi.org/10.1124/mol.113.090530

Enhancement of Current through Trek1 Two Pore Domain Channels by Flufenamic Acid
Ehab Al-Moubarak and Alistair Mathie 2014. Enhancement of Current through Trek1 Two Pore Domain Channels by Flufenamic Acid. Biophysical Journal. 106 (2, supplement 1), p. 748A. https://doi.org/10.1016/j.bpj.2013.11.4121

GuideToPharmacology.org - An update
Alexander, S.P.H., Benson, H.E., Davenport, A., Mathie, A., McGrath, I.J.C., Pawson, A.J., Peters, J.A., Sharman, J.L., Spedding, M. and Harmar, A.J. 2012. GuideToPharmacology.org - An update. British Journal of Pharmacology. 167 (4), pp. 697-698. https://doi.org/10.1111/j.1476-5381.2012.02141.x

Guide to Receptors and Channels (GRAC), 5th edition
Alexander, S.P., Mathie, A. and Peters, J.A. 2011. Guide to Receptors and Channels (GRAC), 5th edition. British Journal of Pharmacology. 164 (S1). https://doi.org/10.1111/j.1476-5381.2011.01649_1.x

Ion channels as novel therapeutic targets in the treatment of pain
Mathie, A. 2010. Ion channels as novel therapeutic targets in the treatment of pain. Journal of Pharmacy and Pharmacology. 62 (9), pp. 1089-1095. https://doi.org/10.1111/j.2042-7158.2010.01131.x

Dominant negative effects of a non-conducting TREK1 splice variant expressed in brain
Veale, E.L., Rees, K.A., Mathie, A. and Trapp, S. 2010. Dominant negative effects of a non-conducting TREK1 splice variant expressed in brain. Journal of Biological Chemistry. 285 (38), pp. P29295-29304. https://doi.org/10.1074/jbc.m110.108423

Trafficking of neuronal two pore domain potassium channels
Mathie, A., Rees, K.A., El Hachmane, M.F. and Veale, E.L. 2010. Trafficking of neuronal two pore domain potassium channels. Current Neuropharmacology. 8 (3), pp. 276-286. https://doi.org/10.2174/157015910792246146

Symposium Review: Gating of two pore domain potassium channels
Mathie, A., Al-Moubarak, E. and Veale, E.L. 2010. Symposium Review: Gating of two pore domain potassium channels. Journal of Physiology. 588 (17), pp. 3149-3156. https://doi.org/10.1113/jphysiol.2010.192344

Guide to Receptors and Channels (GRAC), 4th edition
Alexander, S.P.H., Mathie, A. and Peters, J.A. 2009. Guide to Receptors and Channels (GRAC), 4th edition. British Journal of Pharmacology. 158 (S1). https://doi.org/10.1111/j.1476-5381.2009.00499.x

Neuronal Potassium Channels
Alistair Mathie and Emma L. Veale 2009. Neuronal Potassium Channels. in: Binder, M.D., Hirokawa, N. and Windhorst, U. (ed.) Encyclopedia of Neuroscience Springer Nature. pp. 2792–2797

Guide to Receptors and Channels (GRAC), 3rd edition
Alexander, S.P.H., Mathie, A. and Peters, J.A. 2008. Guide to Receptors and Channels (GRAC), 3rd edition. British Journal of Pharmacology. 153 (Suppl. 2), p. S1–S209. https://doi.org/10.1038/sj.bjp.0707746

The M1P1 loop of TASK3 K2P channels apposes the selectivity filter and influences channel function
Clarke, C.E., Veale, E.L., Wyse, K., Vandenberg, J.I. and Mathie, A. 2008. The M1P1 loop of TASK3 K2P channels apposes the selectivity filter and influences channel function. Journal of Biological Chemistry. 283 (25), pp. 16985-16992. https://doi.org/10.1074/jbc.m801368200

Neuronal two-pore-domain potassium channels and their regulation by G protein-coupled receptors
Mathie, A. 2007. Neuronal two-pore-domain potassium channels and their regulation by G protein-coupled receptors. Journal of Physiology. 278 (2), pp. 377-385. https://doi.org/10.1113/jphysiol.2006.121582

Guide to Receptors and Channels (GRAC), 2nd edition
Alexander, S.P.H., Mathie, A. and Peters, J.A. 2007. Guide to Receptors and Channels (GRAC), 2nd edition. British Journal of Pharmacology. 150 (S1). https://doi.org/10.1038/sj.bjp.0707199

Gαq-Mediated Regulation of TASK3 Two-Pore Domain Potassium Channels: The Role of Protein Kinase C
Veale, E.L., Kennard, L.E., Sutton, G.L., MacKenzie, G., Sandu, C. and Mathie, A. 2007. Gαq-Mediated Regulation of TASK3 Two-Pore Domain Potassium Channels: The Role of Protein Kinase C. Molecular Pharmacology. 71 (6), pp. 1666-1675. https://doi.org/10.1124/mol.106.033241

TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons
Brickley, S.G., Aller, M.I., Sandu, C., Veale, E.L., Alder, F.G., Sambi, H., Mathie, A. and Wisden, W. 2007. TASK-3 two-pore domain potassium channels enable sustained high-frequency firing in cerebellar granule neurons. Journal of Neuroscience. 27 (35), pp. 9329-9340. https://doi.org/10.1523/jneurosci.1427-07.2007

Identification of a region in the TASK3 two pore domain potassium channel that is critical for its blockade by methanandamide
Veale, E.L., Buswell, R., Clarke, C.E. and Mathie, A. 2007. Identification of a region in the TASK3 two pore domain potassium channel that is critical for its blockade by methanandamide. British Journal of Pharmacology. 152 (5), pp. 778-786. https://doi.org/10.1038/sj.bjp.0707436

Therapeutic potential of neuronal two-pore domain potassium-channel modulators
Mathie, A. and Veale, E.L. 2007. Therapeutic potential of neuronal two-pore domain potassium-channel modulators. Current Opinion in Investigational Drugs. 8 (7), pp. 555-562.

The in Vivo Contributions of TASK-1-Containing Channels to the Actions of Inhalation Anesthetics, the α2 Adrenergic Sedative Dexmedetomidine, and Cannabinoid Agonists
Linden, A.-M., Aller, M.I., Leppä, E., Vekovischeva, O., Aitta-Aho, T., Veale, E.L., Mathie, A., Rosenberg, P., Wisden, W. and Korpi, E.R. 2006. The in Vivo Contributions of TASK-1-Containing Channels to the Actions of Inhalation Anesthetics, the α2 Adrenergic Sedative Dexmedetomidine, and Cannabinoid Agonists. Journal of Pharmacology and Experimental Therapeutics. 317 (2), pp. 615-626. https://doi.org/10.1124/jpet.105.098525

Zinc and copper: Pharmacological probes and endogenous modulators of neuronal excitability
Mathie, A., Sutton, G.L., Clarke, C.E. and Veale, E.L. 2006. Zinc and copper: Pharmacological probes and endogenous modulators of neuronal excitability. Pharmacology & Therapeutics. 111 (3), pp. 567-583. https://doi.org/10.1016/j.pharmthera.2005.11.004

Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine
Kennard, L.E., Chumbley, J.R., Ranatunga, K.M., Armstrong, S.J., Veale, E.L. and Mathie, A. 2005. Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine. British Journal of Pharmacology. 144, pp. 821-829. https://doi.org/10.1038/sj.bjp.0706068

Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons
Aller, M.I., Veale, E.L., Linden, A.-M., Sandu, C., Schwaninger, M., Evans, L.J., Korpi, E.R., Mathie, A., Wisden, W. and Brickley, S.G. 2005. Modifying the subunit composition of TASK channels alters the modulation of a leak conductance in cerebellar granule neurons. Journal of Neuroscience. 25 (49), pp. 11455-11467. https://doi.org/10.1523/jneurosci.3153-05.2005

Two-Pore-Domain Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane
Gruss, M., Bushell, T.J., Bright, D.P., Lieb, W.R., Mathie, A. and Franks, N.P. 2004. Two-Pore-Domain Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane. Molecular Pharmacology. 65 (2), pp. 443-452. https://doi.org/10.1124/mol.65.2.443

Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc
Clarke, C.E., Veale, E.L., Green, P.J., Meadows, H.J. and Mathie, A. 2004. Selective block of the human 2-P domain potassium channel, TASK-3, and the native leak potassium current, IKSO, by zinc. Journal of Physiology. 560 (1), pp. 51-62. https://doi.org/10.1113/jphysiol.2004.070292

Guide to receptors and channels. 1st edition (2005 revision)
Alexander, S.P., Mathie, A. and Peters, J.A. 2004. Guide to receptors and channels. 1st edition (2005 revision). British Journal of Pharmacology. 144 (S1). https://doi.org/10.1038/sj.bjp.0706158

What are the roles of the many different types of potassium channel expressed in cerebellar granule cells?
Mathie, A., Clarke, C.E., Ranatunga, K.M. and Veale, E.L. 2003. What are the roles of the many different types of potassium channel expressed in cerebellar granule cells? The Cerebellum. 2, pp. 11-25. https://doi.org/10.1080/14734220310015593

Neuronal ion channels and their sensitivity to extremely low frequency weak electric field effects.
Mathie, A., Kennard, L.E. and Veale, E.L. 2003. Neuronal ion channels and their sensitivity to extremely low frequency weak electric field effects. Radiation Protection Dosimetry. 106 (4), pp. 311-315. https://doi.org/10.1093/oxfordjournals.rpd.a006365

Inhibition of the potassium current IKSO, in cerebellar granule cells, by the inhibitors of MEK1 activation, PD 98059 and U 0126
Boyd, D.F. and Mathie, A. 2002. Inhibition of the potassium current IKSO, in cerebellar granule cells, by the inhibitors of MEK1 activation, PD 98059 and U 0126. Neuropharmacology. 42 (2), pp. 221-228. https://doi.org/10.1016/s0028-3908(01)00168-x

Pharmacological characterization of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones.
Bushell, T., Clarke, C., Mathie, A. and Robertson, B. 2002. Pharmacological characterization of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones. British Journal of Pharmacology. 135, pp. 705-712. https://doi.org/10.1038/sj.bjp.0704518

Background potassium channels move into focus
Mathie, A. and Clarke, C.E. 2002. Background potassium channels move into focus. Journal of Physiology. 542 (2), p. 334. https://doi.org/10.1113/jphysiol.2002.020008

Mammalian Two-Pore Domain Potassium Channels
Alistair Mathie and Brian Robertson 2001. Mammalian Two-Pore Domain Potassium Channels. Physiology News. 43. https://doi.org/10.36866/pn.43.5

TiPS nomenclature supplement 2001
Steve Alexander, Alistair Mathie, John Peters, Gillian MacKenzie and Adam Smith 2001. TiPS nomenclature supplement 2001. Trends in Pharmacological Sciences. 22 (s1). https://doi.org/10.1016/s0165-6147(01)80001-8

Inhibition of delayed rectifier K+ conductance in cultured rat cerebellar granule neurons by activation of calcium-permeable AMPA receptors
Jones, G., Boyd, D.F., Yeung, S.Y. and Mathie, A. 2000. Inhibition of delayed rectifier K+ conductance in cultured rat cerebellar granule neurons by activation of calcium-permeable AMPA receptors. European Journal of Neuroscience. 12 (3), pp. 935-944. https://doi.org/10.1046/j.1460-9568.2000.00983.x

Purinergic and muscarinic receptor activation activates a common calcium entry pathway in rat neocortical neurons and glial cells
Prothero, L.S., Mathie, A. and Richards, C.D. 2000. Purinergic and muscarinic receptor activation activates a common calcium entry pathway in rat neocortical neurons and glial cells. Neuropharmacology. 39 (10), pp. 1768-1778. https://doi.org/10.1016/s0028-3908(00)00013-7

A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons
Millar, J.A., Barratt, L., Southan, A.P., Page, K.M., Fyffe, R.E., Robertson, B. and Mathie, A. 2000. A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons. Proceedings of the National Academy of Sciences. 97 (7), pp. 3614-3618. https://doi.org/10.1073/pnas.97.7.3614

The role of Ca2+ stores in the muscarinic inhibition of the K+ current IK(SO) in neonatal rat cerebellar granule cells
Boyd, D.F., Millar, J.A., Watkins, C.S. and Mathie, A. 2000. The role of Ca2+ stores in the muscarinic inhibition of the K+ current IK(SO) in neonatal rat cerebellar granule cells. Journal of Physiology. 529 (2), pp. 321-331. https://doi.org/10.1111/j.1469-7793.2000.00321.x

Inhibition of neuronal KV potassium currents by the antidepressant drug, fluoxetine
Yeung, S.Y., Millar, J.A. and Mathie, A. 1999. Inhibition of neuronal KV potassium currents by the antidepressant drug, fluoxetine. British Journal of Pharmacology. 128 (7), pp. 1609-1615. https://doi.org/10.1038/sj.bjp.0702955

Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents
Mathie, A., Wooltorton, J.R.A. and Watkins, C.S. 1998. Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents. General Pharmacology: The Vascular System. 30 (1), pp. 13-24. https://doi.org/10.1016/s0306-3623(97)00034-7

Characterization of the hyperpolarization - Activated chloride current in dissociated rat sympathetic neurons
Clark, S., Jordt, S.-E., Jentsch, T.J. and Mathie, A. 1998. Characterization of the hyperpolarization - Activated chloride current in dissociated rat sympathetic neurons. Journal of Physiology. 506 (3), pp. 665-678. https://doi.org/10.1111/j.1469-7793.1998.665bv.x

Activation of group I metabotropic glutamate receptors elicits pH changes in cultured rat cortical glia and neurons
Amos, B.J., Mathie, A. and Richards, C.D. 1998. Activation of group I metabotropic glutamate receptors elicits pH changes in cultured rat cortical glia and neurons. Neuroscience. 86 (4), pp. 1109-1120. https://doi.org/10.1016/s0306-4522(98)00072-4

Inhibition by inorganic ions of a sustained calcium signal evoked by activation of mGlu5 receptors in rat cortical neurons and glia.
Prothero, L.S., Richards, C.D. and Mathie, A. 1998. Inhibition by inorganic ions of a sustained calcium signal evoked by activation of mGlu5 receptors in rat cortical neurons and glia. British Journal of Pharmacology. 125, pp. 1551-1561. https://doi.org/10.1038/sj.bjp.0702203

Is EAG the answer to the M-current?
Mathie, A. and Watkins, C.S. 1997. Is EAG the answer to the M-current? Trends in Neurosciences. 20 (1), p. 14. https://doi.org/10.1016/s0166-2236(96)20057-8

Book review: Ion Channels: Molecules in Action. Edited by D. J. Aidley and P. R. Stanfield . Pp. 340. Cambridge University Press, 1996. £17.95 paperback, ISBN 0521 49882 1. £50.00 hardback, ISBN 0 521 49531 8
Alistair Mathie 1997. Book review: Ion Channels: Molecules in Action. Edited by D. J. Aidley and P. R. Stanfield . Pp. 340. Cambridge University Press, 1996. £17.95 paperback, ISBN 0521 49882 1. £50.00 hardback, ISBN 0 521 49531 8. Experimental Physiology. 109 (4), pp. 607-608. https://doi.org/10.1113/expphysiol.1998.sp004327

A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons.
Watkins, C.S. and Mathie, A. 1996. A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons. Journal of Physiology. 491 (2), pp. 401-412. https://doi.org/10.1113/jphysiol.1996.sp021224

Effects on K+ currents in rat cerebellar granule neurones of a membrane-permeable analogue of the calcium chelator BAPTA
Watkins, C.S. and Mathie, A. 1996. Effects on K+ currents in rat cerebellar granule neurones of a membrane-permeable analogue of the calcium chelator BAPTA. British Journal of Pharmacology. 118 (7), pp. 1772-1778. https://doi.org/10.1111/j.1476-5381.1996.tb15603.x

A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons
Watkins, C.S. and Mathie, A. 1996. A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons. Journal of Physiology. 491 (2), pp. 401-412. https://doi.org/10.1113/jphysiol.1996.sp021224

Book review: Methods in neurosciences volume 19: Ion channels of excitable cells
Mathie, A. 1995. Book review: Methods in neurosciences volume 19: Ion channels of excitable cells. Neuroscience. 64 (3), p. 845. https://doi.org/10.1016/0306-4522(95)90003-9

Multiple G-protein-coupled pathways inhibit N-type Ca channels of neurons
Hille, B., Beech, D.J., Bernheim, L., Mathie, A., Shapiro, M.S. and Wollmuth, L.P. 1995. Multiple G-protein-coupled pathways inhibit N-type Ca channels of neurons. Life Sciences. 56 (11-12), pp. 989-992. https://doi.org/10.1016/0024-3205(95)00038-8

Potent block of potassium currents in rat isolated sympathetic neurones by the uncharged form of amitriptyline and related tricyclic compounds
Wooltorton, J.R. and Mathie, A. 1995. Potent block of potassium currents in rat isolated sympathetic neurones by the uncharged form of amitriptyline and related tricyclic compounds. British Journal of Pharmacology. 116 (4), pp. 2191-2200. https://doi.org/10.1111/j.1476-5381.1995.tb15053.x

Erratum: Block of potassium currents in rat isolated sympathetic neurones by tricyclic antidepressants and structurally related compounds (Br. J. Pharmacol. (1993), 110, 1126-1132)
Wooltorton, J.R.A. and Mathie, A. 1994. Erratum: Block of potassium currents in rat isolated sympathetic neurones by tricyclic antidepressants and structurally related compounds (Br. J. Pharmacol. (1993), 110, 1126-1132). British Journal of Pharmacology. 111 (1), p. 377.

Modulation of the gating of the transient outward potassium current of rat isolated cerebellar granule neurons by lanthanum
Watkins, C.S. and Mathie, A. 1994. Modulation of the gating of the transient outward potassium current of rat isolated cerebellar granule neurons by lanthanum. Pflügers Archiv - European Journal of Physiology. 428, pp. 209-216. https://doi.org/10.1007/bf00724499

The modulation by lanthanum of the gating of voltage-dependent potassium currents in rat isolated cerebellar granule neurones
Watkins, C.S. and Mathie, A. 1993. The modulation by lanthanum of the gating of voltage-dependent potassium currents in rat isolated cerebellar granule neurones. Journal of Physiology. 473, p. 160P.

Block of potassium currents in rat isolated sympathetic neurones by tricyclic antidepressants and structurally related compounds
Wooltorton, J.R. and Mathie, A. 1993. Block of potassium currents in rat isolated sympathetic neurones by tricyclic antidepressants and structurally related compounds. British Journal of Pharmacology. 110 (3), pp. 1126-1132. https://doi.org/10.1111/j.1476-5381.1993.tb13931.x

5‐HT3 receptor channels in dissociated rat superior cervical ganglion neurons
Yang, J., Mathie, A. and Hille, B. 1992. 5‐HT3 receptor channels in dissociated rat superior cervical ganglion neurons. Journal of Physiology. 448 (1), pp. 237-256. https://doi.org/10.1113/jphysiol.1992.sp019039

Classification of muscarinic receptors inhibiting calcium current and M current in dissociated rat superior cervical ganglion (SCG) neurons
Mathie, A., Bernheim, L. and Hille, B. 1992. Classification of muscarinic receptors inhibiting calcium current and M current in dissociated rat superior cervical ganglion (SCG) neurons. Journal of Physiology. 446, p. 548P.

Inhibition of N- and L-type calcium channels by muscarinic receptor activation in rat sympathetic neurons
Mathie, A., Bernheim, L. and Hille, B. 1992. Inhibition of N- and L-type calcium channels by muscarinic receptor activation in rat sympathetic neurons. Neuron. 8 (5), pp. P907-914. https://doi.org/10.1016/0896-6273(92)90205-r

Characterization of muscarinic receptor subtypes inhibiting Ca2+ current and M current in rat sympathetic neurons
Bernheim, L., Mathie, A. and Hille, B. 1992. Characterization of muscarinic receptor subtypes inhibiting Ca2+ current and M current in rat sympathetic neurons. Proceedings of the National Academy of Sciences. 89 (20), pp. 9544-9548. https://doi.org/10.1073/pnas.89.20.9544

Conductance and kinetic properties of single nicotinic acetylcholine receptor channels in rat sympathetic neurones
Mathie, A., Cull‐Candy, S.G. and Colquhoun, D. 1991. Conductance and kinetic properties of single nicotinic acetylcholine receptor channels in rat sympathetic neurones. Journal of Physiology. 439 (1), pp. 717-750. https://doi.org/10.1113/jphysiol.1991.sp018690

Activation of glutamate receptors and glutamate uptake in identified macroglial cells in rat cerebellar cultures.
Wyllie, D.J., Mathie, A., Symonds, C.J. and Cull‐Candy, S.G. 1991. Activation of glutamate receptors and glutamate uptake in identified macroglial cells in rat cerebellar cultures. Journal of Physiology. 432 (1), pp. 235-258. https://doi.org/10.1113/jphysiol.1991.sp018383

Intracellular Ca2+ buffers disrupt muscarinic suppression of Ca2+ current and M current in rat sympathetic neurons
Beech, D.J., Bernheim, L., Mathie, A. and Hille, B. 1991. Intracellular Ca2+ buffers disrupt muscarinic suppression of Ca2+ current and M current in rat sympathetic neurons. Proceedings of the National Academy of Sciences. 88 (2), pp. 652-656. https://doi.org/10.1073/pnas.88.2.652

Function of nicotinic synapses
Colquhoun, D., Cachelin, A.B., Marshall, C.G., Mathie, A. and Ogden, D.C. 1990. Function of nicotinic synapses. in: Aquilonius, S-M. and Gillberg, P-G. (ed.) Cholinergic neurotransmission: functional and clinical aspects. Proceedings of Nobel Symposium 76. Lidingö Island, Stockholm, August 1989 Elsevier. pp. 43-50

Rectification of currents activated by nicotinic acetylcholine receptors in rat sympathetic ganglion neurones.
Mathie, A., Colquhoun, D. and Cull‐Candy, S.G. 1990. Rectification of currents activated by nicotinic acetylcholine receptors in rat sympathetic ganglion neurones. Journal of Physiology. 427 (1), pp. 625-655. https://doi.org/10.1113/jphysiol.1990.sp018191

Studies on single acetylcholine-receptor channels in muscle end-plate and sympathetic neurones
Colquhoun, D., Mathie, A., Mulrine, N.K. and Ogden, D.C. 1989. Studies on single acetylcholine-receptor channels in muscle end-plate and sympathetic neurones. Fernstrom Foundation Series. 13, pp. 217-234.

Acetylcholine receptor channels and their block by clonidine in cultured bovine chromaffin cells.
Cull‐Candy, S.G., Mathie, A. and Powis, D.A. 1988. Acetylcholine receptor channels and their block by clonidine in cultured bovine chromaffin cells. Journal of Physiology. 402 (1), pp. 255-278. https://doi.org/10.1113/jphysiol.1988.sp017203

Nicotinic acetylcholine receptors of nerve and muscle: Functional aspects
David Colquhoun, David C. Ogden and Alistair Mathie 1987. Nicotinic acetylcholine receptors of nerve and muscle: Functional aspects. Trends in Pharmacological Sciences. 8 (12), pp. 465-472. https://doi.org/10.1016/0165-6147(87)90040-x

Single-channel and whole-cell currents evoked by acetylcholine in dissociated sympathetic neurons of the rat
Mathie, A., Cull-Candy, S.G. and Colquhoun, D. 1987. Single-channel and whole-cell currents evoked by acetylcholine in dissociated sympathetic neurons of the rat. Proceedings of the Royal Society B: Biological Sciences. 232 (1267), pp. 239-248. https://doi.org/10.1098/rspb.1987.0072

Interactions between the effects of yohimbine, clonidine and [Ca]o on the electrical response of the mouse vas deferens
Blakeley, A.G., Mathie, A. and Petersen, S.A. 1986. Interactions between the effects of yohimbine, clonidine and [Ca]o on the electrical response of the mouse vas deferens. British Journal of Pharmacology. 88 (4), pp. 807-814. https://doi.org/10.1111/j.1476-5381.1986.tb16253.x

Ion channels activated by acetylcholine and gamma-aminobutyric acid in freshly dissociated sympathetic neurones of the rat.
Cull-Candy, S.G. and Mathie, A. 1986. Ion channels activated by acetylcholine and gamma-aminobutyric acid in freshly dissociated sympathetic neurones of the rat. Neuroscience Letters. 66 (3), pp. 275-280. https://doi.org/10.1016/0304-3940(86)90031-5

Alpha-adrenoceptors and facilitation at a sympathetic neuroeffector junction
Blakeley, A.G., Cunnane, T.C., Maskell, T., Mathie, A. and Petersen, S.A. 1984. Alpha-adrenoceptors and facilitation at a sympathetic neuroeffector junction. Journal of Autonomic Pharmacology. 4 (1), pp. 53-58. https://doi.org/10.1111/j.1474-8673.1984.tb00433.x

Facilitation at single release sites of a sympathetic neuroeffector junction in the mouse.
Blakeley, A.G., Mathie, A. and Petersen, S.A. 1984. Facilitation at single release sites of a sympathetic neuroeffector junction in the mouse. Journal of Physiology. 349 (1), pp. 57-71. https://doi.org/10.1113/jphysiol.1984.sp015142

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