Staff Profile:Professor Gary Stephens

Name:

Professor Gary Stephens

Job Title:

Professor of Pharmacology

Responsibilities:

Director of Pharmacology and Therapeutics

Areas of Interest:

Synaptic transmission is triggered when calcium ions enter presynaptic terminals via voltage-gated calcium channels. Calcium influx leads to a series of protein-protein interactions resulting in the release of neurotransmitters from vesicles into the synaptic cleft. Neurotransmitters can interact with postsynaptic receptors or, by feedback, with presynaptic receptors present on nerve terminals. Our group uses patch clamp electrophysiology to investigate presynaptic mechanisms in synaptic transmission. In particular, we are interested in modulation of presynaptic calcium channels and G protein-coupled receptor (GPCR). We are also investigating the molecular determinants in the modulation of ion channels and receptors and in inhibitory synaptic transmission in the mammalian cerebellum, and have extended this work to excitatory transmission in hippocampal brain slices. Our current focus here is on plant derived cannabinoids, which we are investigating using electrophysiological recordings from brain slices. In addition, we investigate ion channel and GPCR modulation in native neurones and recombinant cells.

Research interests:

• Modulation of calcium channels by intracellular antibodies 'intrabodies' (UCB Pharma funded project with Prof Ben Whalley, University of Reading)

• Functional effects of CACHD1 on calcium channels (with Pfizer Neusentis UK)

• SUMOylation of calcium channels (with Dr Helena Cimarosti, Universidade Federal de Santa Catarina (UFSC), Brazil and Prof Sumiko Mochida, Tokyo Medical University, Japan)

• Mechanism of action of synaptic vesicle 2A ligands (with Prof Ben Whalley, University of Reading and Prof Sumiko Mochida, Tokyo Medical University)

• Role of plant cannabinoids in hyperexcitability in the CNS (with Prof Claire Williams and Prof Ben Whalley, University of Reading)

• Modulation of inhibitory neurotransmission in the cerebellum

Memberships:

• Co-Chair British Pharmacological Society Molecular & Cellular Pharmacology Affinity Group

• British Journal of Pharmacology Editorial Board

• British Pharmacological Society Committee of Heads and Professors of Pharmacology & Therapeutics (CHOPT)

• The Physiological Society (University of Reading representative).

• The Calcium Channel Network (http://www.calciumchannel.com/about/)

• Pharmaceuticals Editorial Board

Research groups / Centres:

School of Pharmacy, Pharmacology Group, Electrophysiology and Behavioural Neuroscience Group; Centre for Neuroscience and Neurodynamics

Publications:

Y

Jump to: 2018 | 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005

Number of items: 38.

2018

• Stevens, E. B. and Stephens, G. J., eds. (2018) Recent advances in targeting ion channels to treat chronic pain. British Journal of Pharmacology, 175 (12). Wiley, pp. 2133-2137. doi: https://doi.org/10.1111/bph.14215
• Whalley, B. J., Lin, H., Bell, L., Hill, T., Patel, A., Gray, R. A., Roberts, E., Devinsky, O., Bazelot, M., Williams, C. M. and Stephens, G. J. (2018) Species-specific susceptibility to cannabis-induced convulsions. British Journal of Pharmacology. ISSN 0007-1188 doi: https://doi.org/10.1111/bph.14165 (In Press)

2017

• Coelho-Silva, L., Stephens, G. J. and Cimarosti, H. (2017) SUMOylation and calcium signalling: potential roles in the brain and beyond. Neuronal Signaling, 1 (3). NS20160010. ISSN 2059-6553 doi: https://doi.org/10.1042/NS20160010
• Arjmand, S. , Behzadi, M., Stephens, G. J., Ezzatabadipou, S. , Seifaddini, R. , Arjmand, S. and Shabani, M. (2017) A brain on a roller coaster: can the dopamine reward system act as a protagonist to subdue the ups and downs of bipolar disorder? The Neuroscientist. ISSN 1073-8584 doi: https://doi.org/10.1177/1073858417714226
• Barker, B. S. , Young , G. T. , Soubrane, C. H., Stephens, G. J., Stevens, E. B. and Patel , M. K. (2017) Ion channels. In: Conn, P. M. (ed.) Conn's Translational Neuroscience 1st Edition. Elsevier Academic Press, London, pp. 11-43. ISBN 9780128023815

2016

• Heath, F., Newman, A., Clementi, C., Pasut, G., Lin, H., Stephens, G. J., Whalley, B. J., Osborn, H. M. I. and Greco, F. (2016) A novel PEG–haloperidol conjugate with a non-degradable linker shows the feasibility of using polymer–drug conjugates in a non-prodrug fashion. Polymer Chemistry, 7 (47). pp. 7204-7210. ISSN 1759-9954 doi: https://doi.org/10.1039/c6py01418f
• Stephens, G. J. (2016) Does modulation of the endocannabinoid system have potential therapeutic utility in cerebellar ataxia? Journal of Physiology, 594 (16). pp. 4631-4641. ISSN 1469-7793 doi: https://doi.org/10.1113/JP271106
• Stephens, G. J. (2016) Cerebellar circuits: biochemistry, neurotransmitters and neuromodulators: cannabinoids as modulators in the cerebellum. In: Gruol, D. L., Koibuchi, N., Manto, M., Molinari, M., Schmahmann, J. D. and Shen, Y. (eds.) Essentials of Cerebellum and Cerebellar Disorders: A Primer For Graduate Students. Springer, Dordrecht, pp. 255-259. ISBN 9783319245492 doi: https://doi.org/10.1007/978-3-319-24551-5_33

2015

• Arjmand, S., Vaziri, Z., Behzadi, M., Abbassian, H., Stephens, G. J. and Shabani, M. (2015) Cannabinoids and tremor induced by motor-related disorders: friend or foe? Neurotherapeutics, 12 (4). pp. 778-787. ISSN 1933-7213 doi: https://doi.org/10.1007/s13311-015-0367-5
• Ronzitti, G., Bucci, G., Stephens, G. and Chieregatti, E. (2015) Raft-partitioning of calcium channels regulates their function. Channels, 9 (4). pp. 169-170. ISSN 1933-6969 doi: https://doi.org/10.1080/19336950.2015.1063285
• Vogl, C., Tanifuji, S., Danis, B., Daniels, V., Foerch, P., Wolff, C., Whalley, B. J., Mochida, S. and Stephens, G. J. (2015) Synaptic vesicle glycoprotein 2A modulates vesicular release and calcium channel function at peripheral sympathetic synapses. The European Journal of Neuroscience, 41 (4). pp. 398-409. ISSN 0953-816X doi: https://doi.org/10.1111/ejn.12799

2014

• Ronzitti, G., Bucci, G., Emanuele, M., Leo, D., Sotnikova, T. D., Mus, L. V., Soubrane, C. H., Dallas, M. L., Thalhammer, A., Cingolani, L. A., Mochida, S., Gainetdinov, R. R., Stephens, G. J. and Chieregatti, E. (2014) Exogenous alpha-Synuclein decreases raft partitioning of Cav2.2 channels inducing dopamine release. Journal of Neuroscience, 34 (32). pp. 10603-10615. ISSN 1529-2401 doi: https://doi.org/10.1523/JNEUROSCI.0608-14.2014
• Iannotti, F. A., Hill, C. L., Leo, A., Alhusaini, A., Soubrane, C., Mazzarella, E., Russo, E., Whalley, B. J., Di Marzo, V. and Stephens, G. J. (2014) Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chemical Neuroscience, 5 (11). pp. 1131-1141. ISSN 1948-7193 doi: https://doi.org/10.1021/cn5000524
• Hill, A., Jones, N., Smith, I., Hill, C., Williams, C., Stephens, G. and Whalley, B. (2014) Voltage-gated sodium (NaV) channel blockade by plant cannabinoids does not confer anticonvulsant effects per se. Neuroscience Letters, 566. pp. 269-274. ISSN 0304-3940 doi: https://doi.org/10.1016/j.neulet.2014.03.013

2013

• Wang, X., Whalley, B. J. and Stephens, G. J. (2013) The du2J mouse model of ataxia and absence epilepsy has deficient cannabinoid CB1 receptor-mediated signalling. Journal of Physiology, 591 (16). pp. 3919-3933. ISSN 1469-7793 doi: https://doi.org/10.1113/jphysiol.2012.244947
• Silveirinha, V., Stephens, G. J. and Cimarosti, H. (2013) Molecular targets underlying SUMO-mediated neuroprotection in brain ischemia. Journal of Neurochemistry, 127 (5). pp. 580-591. ISSN 0022-3042 doi: https://doi.org/10.1111/jnc.12347
• Bucci, G., Mochida, S. and Stephens, G. (2013) Use of synthetic CaV2.2 Ca2+ channel peptides to study presynaptic function. In: Stephens, G. and Mochida, S. (eds.) Modulation of Presynaptic Calcium Channels. Springer, Dordrecht, pp. 223-240. ISBN 9789400763333 doi: https://doi.org/10.1007/978-94-007-6334-0
• Baillie, G. L. , Horswill, J., Anavi-Goffer,, S. , Reggio, P. H. , Bolognini , D. , Abood, M. E. , McAllister, S. , Strange, P., Stephens, G., Pertwee, R. G. and Ross, R. A. (2013) CB1 receptor allosteric modulators display both agonist and signaling pathway specificity. Molecular Pharmacology, 82 (2). pp. 322-338. ISSN 1521-0111 doi: https://doi.org/10.1124/mol.112.080879

2012

• Hill, A. J., Mercier, M. S., Hill, T. D., Glyn, S. E., Jones, N. A., Yamasaki, Y., Futamura, T., Duncan, M., Stott, C.G., Stephens, G.J., Williams, C. M. and Whalley, B.J. (2012) Cannabidivarin is anticonvulsant in mouse and rat in vitro and in seizure models. British Journal of Pharmacology, 167 (8). pp. 1629-1642. ISSN 0007-1188 doi: https://doi.org/10.1111/j.1476-5381.2012.02207.x
• Jones, N. A., Glyn, S. E., Akiyama, S., Hill, T. D. M., Hill, A. J., Weston, S. E., Burnett, M. D. A., Yamasaki, Y., Stephens, G. J., Whalley, B. J. and Williams, C. M. (2012) Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure, 21 (5). pp. 344-352. ISSN 1059-1311 doi: https://doi.org/10.1016/j.seizure.2012.03.001
• Hill, A. J., Williams, C. M., Whalley, B. J. and Stephens, G. J. (2012) Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacology & Therapeutics, 133 (1). pp. 79-97. ISSN 0163-7258 doi: https://doi.org/10.1016/j.pharmthera.2011.09.002
• Vogl, C., Mochida, S., Wolff, C., Whalley, B. and Stephens, G. (2012) The SV2A ligand levetiracetam inhibits presynaptic Ca2+ channels via an intracellular pathway. Molecular Pharmacology, 82 (2). pp. 199-208. ISSN 1521-0111 doi: https://doi.org/10.1124/mol.111.076687

2011

• Bucci, G., Mochida, S. and Stephens, G. J. (2011) Inhibition of synaptic transmission and G protein modulation by synthetic CaV2.2 Ca2+ channel peptides. Journal of Physiology, 589 (13). pp. 3085-3101. ISSN 0022-3751 doi: https://doi.org/10.1113/jphysiol.2010.204735
• Wang, X., Horswill, J. G., Whalley, B. J. and Stephens, G. J. (2011) Effects of the Allosteric Antagonist 1-(4-Chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea (PSNCBAM-1) on CB1 Receptor Modulation in the Cerebellum. Molecular Pharmacology, 79 (4). pp. 758-767. ISSN 1521-0111 doi: https://doi.org/10.1124/mol.110.068197

2010

• Hill, A. J., Weston, S. E., Jones, N., Smith, I., Bevan , S., Williamson, E. M., Stephens, G. J., Williams, C. M. and Whalley, B. J. (2010) Δ9-tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rat. Epilepsia, 51 (8). pp. 1522-1532. ISSN 0013-9580 doi: https://doi.org/10.1111/j.1528-1167.2010.02523.x
• Jones, N. A., Hill, A. J., Smith, I., Bevan, S. A., Williams, C. M., Whalley, B. J. and Stephens, G. J. (2010) Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. Journal of Pharmacology and Experimental Therapeutics, 332 (2). pp. 569-577. ISSN 0022-3565 doi: https://doi.org/10.1124/jpet.109.159145
• Hill, A. J., Jones, N., Williams, C. M., Stephens, G. J. and Whalley, B. J. (2010) Development of multi-electrode array screening for anticonvulsants in acute rat brain slices. Journal of Neuroscience Methods, 185 (2). 246 -256 . ISSN 0165-0270 doi: https://doi.org/10.1016/j.jneumeth.2009.10.007

2009

• Yang, L. and Stephens, G. J. (2009) Effects of neuropathy on high-voltage-activated Ca2+ current in sensory neurones. Cell Calcium, 46 (4). 248-256 . ISSN 01434160 doi: https://doi.org/10.1016/j.ceca.2009.08.001
• Stephens, G. J. (2009) G-protein-coupled-receptor-mediated presynaptic inhibition in the cerebellum. Trends in Pharmacological Sciences, 30 (8). 421-430 . ISSN 01656147 doi: https://doi.org/10.1016/j.tips.2009.05.008
• Long, P., Mercer, A., Begum, R., Stephens, G. J., Sihra, T. and Jovanovic, J. (2009) Nerve terminal GABAA receptors activate Ca2+/calmodulin-dependent signaling to inhibit voltage-gated Ca2+ influx and glutamate release. The Journal of Biological Chemistry, 284 (13). pp. 8717-8728. ISSN 1083-351X doi: https://doi.org/10.1074/jbc.M805322200
• Whalley, B. J., Stephens, G. J. and Constanti, A. (2009) Investigation of the effects of the novel anticonvulsant compound carisbamate(RWJ-333369) on rat piriform cortical neurones in vitro. British Journal of Pharmacology, 156 (6). pp. 994-1008. ISSN 0007-1188 doi: https://doi.org/10.1111/j.1476-5381.2008.00110.x
• Farrimond, J., Hill, A. J., Jones, N., Stephens, G. J., Whalley, B. J. and Williams, C. M. (2009) A cost-effective high-throughput digital system for observation and acquisition of animal behavioral data. Behavior Research Methods, 41 (2). pp. 446-451. ISSN 1554-351X doi: https://doi.org/10.3758/BRM.41.2.446

2008

• Dennis, I., Whalley, B. J. and Stephens, G. J. (2008) Effects of Delta9-tetrahydrocannabivarin on [35S]GTPgammaS binding in mouse brain cerebellum and piriform cortex membranes. British Journal of Pharmacology, 154 (6). pp. 1349-58. ISSN 0007-1188 doi: https://doi.org/10.1038/bjp.2008.190
• Ma, Y.-L., Weston, S.E., Whalley, B.J. and Stephens, G.J. (2008) The phytocannabinoid Δ9-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum. British Journal of Pharmacology, 154 (1). pp. 204-215. ISSN 0007-1188 doi: https://doi.org/10.1038/bjp.2008.57

2007

• Matthews, E.A., Bee, L.A., Stephens, G.J. and Dickenson, A.H. (2007) The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain. European Journal of Neuroscience, 25 (12). pp. 3561-3569. ISSN 0953-816X doi: https://doi.org/10.1111/j.1460-9568.2007.05605.x

2006

• Harvey, V.L., Duguid, I.C., Krasel, C. and Stephens, G.J. (2006) Evidence that GABA rho subunits contribute to functional ionotropic GABA receptors in mouse cerebellar Purkinje cells. Journal of Physiology-London, 577 (1). pp. 127-139. ISSN 0022-3751 doi: https://doi.org/10.1113/jphysiol.2006.112482
• Weston, S. E., Williamson, E. M., Constanti, A., Stephens, G. J. and Whalley, B. J. (2006) Tetrahydrocannabivarin exhibits anticonvulsant effects in a piriform cortical brain slice model of epileptiform activity. In: British Pharmacological Society Winter Meeting 2006.

2005

• Stephens, G.J. and Mochida, S. (2005) G protein ss gamma subunits mediate presynaptic inhibition of transmitter release from rat superior cervical ganglion neurones in culture. Journal of Physiology, 563 (3). pp. 765-776. ISSN 0022-3751 doi: https://doi.org/10.1113/jphysiol.2004.080192

This list was generated on Mon Jun 18 06:01:07 2018 UTC.

Research Group members

Post-Doctoral Research Fellows

Dr Giovanna Bucci g.bucci@reading.ac.uk

Dr Andrew Hill a.j.hill@reading.ac.uk

 

PhD Research Students

Nicholas Jones n.a.jones@reading.ac.uk

Camille Soubrane camille.soubrane@reading.ac.uk

 Vasco Silveirinha v.silveirinha@reading.ac.uk

Charlotte Hill c.l.hill@pgr.reading.ac.uk

Other Publications

Harvey, V.L & Stephens, G.J. (2004) Mechanism of GABA_B receptor-mediated inhibition of spontaneous GABA release onto cerebellar Purkinje cells. Eur. J. Neurosci. 20: 684-690

Bardo, S., Robertson, B. & Stephens, G.J. (2002) Presynaptic internal Ca²⁺ stores contribute to inhibitory neurotransmitter release onto mouse cerebellar Purkinje cells. Br. J. Pharmacol. 137: 529-537

Stephens, G.J., Morris, N. P., Fyffe, R. E.W. & Robertson B. (2001) The Ca_V2.1/α1A (P/Q-type) voltage-dependent calcium channel mediates inhibitory neurotransmission onto mouse cerebellar Purkinje cells. Eur. J. Neurosci. 13: 1902-1912

Southan, A.P., Morris, N.P., Stephens, G.J. & Robertson, B. (2000) Hyperpolarization-activated currents in presynaptic terminals of mouse cerebellar basket cells. J. Physiol. 526: 91-97

Stephens, G.J., Page, K.M., Bogdanov Y. & Dolphin, A.C. (2000). The a1B Ca²⁺ channel amino terminus contributes determinants for β subunit-mediated voltage-dependent inactivation properties. J. Physiol. 525: 377-390

Meir, A., Bell, D.C. Stephens, G.J., Page K.M. & Dolphin, A.C (2000) Calcium channel β subunit promotes voltage-dependent modulation of α1B by Gβγ. Biophys. J. 79: 731-746

Canti, C., Page, K.M., Stephens, G.J., & Dolphin, A.C (1999) Identification of amino acids in the N terminus of the rabbit α1B voltage-dependent calcium channel required for inhibition by G proteins. J. Neurosci. 19:6855-6884

Page, K.M., Canti C., Stephens, G.J., Berrow, N.S. & Dolphin, A.C. (1998) Identification of the amino terminus of neuronal Ca²⁺ channel α1 subunits α1B and α1E as an essential determinant of G protein modulation. J. Neurosci. 18: 4815-4824

Stephens, G.J., Canti C., Page, K.M. & Dolphin, A.C. (1998) Role of domain I of neuronal Ca²⁺ channel a1 subunits in G protein modulation. J. Physiol. 509: 163-169.

Stephens, G.J., Brice N.L., Berrow, N.S. & Dolphin, A.C. (1998) Facilitation of α1B calcium channels: involvement of endogenous Gβγ subunits. J. Physiol. 509: 15-27

Owen, D.G., Hall, A., Stephens, G.J., Stow, J. & Robertson, B. (1997) The relative potencies of dendrotoxins as blockers of the cloned voltage-gated K⁺ channel, mKv1.1 (MK-1), when stably expressed in Chinese hamster ovary cells. Br. J. Pharmacol. 120: 1029-1034

Page, K.M., Stephens, G.J., Berrow, N. & Dolphin, A.C. (1997) The intracellular loop between domains I and II of the B-type calcium channel confers aspects of G protein sensistivity to the E-type calcium channel. J. Neurosci. 17: 1330-1338

Stephens, G.J., Page, K.M, Burley, J.R., Berrow, N. & Dolphin, A.C. (1997) Functional expression of rat brain cloned α1E calcium channels in COS-7. Pflügers Archives Eur. J. Physiol 433:523-532

Owen DG,, Hall A, Stephens GJ, Stow J & Robertson B (1997). The relative potencies of dendrotoxins as blockers of the cloned voltage-gated K+ channel, mKv1.1 (MK-1), when stably expressed in Chinese hamster ovary cells. Br. J. Pharmacol. 120:1029-1034

Page, K.M., Stephens, G.J., Berrow, N. & Dolphin, A.C. (1997) The intracellular loop between domains I and II of the B-type calcium channel confers aspects of G protein sensistivity to the E-type calcium channel. J. Neurosci. 17:1330-1338

Stephens, G.J., Owen, D.G., Opalko, A., Pisano, M. R., MacGregor, W. H. & Robertson, B. (1996) Studies on the blocking action of human Kv3.4 inactivation peptide variants in the mouse cloned Kv1.1 K+ channel. J. Physiol. 496:145-154

Stephens, G.J., Owen, D.G. & Robertson, B. (1996) Cysteine-modifying reagents alter the gating of the rat cloned potassium channel Kv1.4. Pflügers Archives Eur. J. Physiol. 431:435-442

Stephens, G.J., Cockett, M. I., Nawoschik, S.P., Schechter, L.E. & Owen, D.G. (1996). The modulation of the rate of inactivation of the mKv1.1 K⁺ channel by the β subunit, Kvβ1 and lack of effect of a Kv_1 N-terminal peptide. FEBS Letts. 378:250-252

Stephens, G.J. & Robertson, B. (1995). Inactivation of the cloned potassium channel, mouse Kv1.1 by the human Kv3.4 'ball' peptide and its chemical modification. J. Physiol. 484:1-13

Grimes JA., Fraser SP, Stephens GJ, Downing JEG, Laniado ME,, Foster CS, Abel PD & Djamgo, MBA (1995). Differential expression of voltage-activated Na+ currents in two prostatic tumour cell lines: contribution to invasiness in vitro. FEBS Letts. 369:290-294

Stephens, G.J., Garratt, J. C., Robertson, B. & Owen, D.G. (1994). On the mechanism of 4-aminopyridine action on the cloned mouse brain potassium channel, mKv1.1. J. Physiol. 477:187-196

Stephens, G.J., Marriott, D.R., Djamgoz, M.B.A. & Wilkin, G.P. (1993) Electrophysiological and biochemical evidence for bradykinin receptors on cultured cortical oligodendrocytes. Neurosci. Lett., 153:223-226

Stephens, G.J., Djamgoz, M.B.A. & Wilkin, G.P. (1993) A patch clamp study of excitatory amino acid effects on cortical astrocyte subtypes in culture. Receptors Channels, 1:39-52

Stephens, G.J., Cholewinski, A.J., Wilkin, G.P. & Djamgoz, M.B.A. (1993) Calcium-mobilizing and electrophysiological effects of bradykinin on cortical astrocyte subtypes in culture. Glia 9:269-279

Wilkin, G.P., Marriott, D.R., Cholewinski, A.J., Wood, J.N., Taylor, G.W., Stephens, G.J. & Djamgoz, M.B.A. (1991) Receptor activation and its biochemical consequences in astrocytes. In: Glial-Neuronal Interaction, Vol. 633. N.J. Abbott, ed. Ann. N. Y. Acad. Sci., New York, pp. 475-488

Cholewinski, A.J., Stephens, G.J., McDermott, A.M. & Wilkin, G.P. (1991) Identification of bradykinin B2 binding sites on cultured cortical astrocytes. J. Neurochem., 57:1456-1458