Staff Profile:Dr Gary Stephens

Name:

Dr Gary Stephens

Job Title:

Director of Pharmacology and Therapeutics

Responsibilities:

Director of Pharmacology and Therapeutics

Areas of Interest:

Synaptic transmission is triggered when calcium ions enter presynaptic terminals via voltage-dependent calcium channels (VDCCs). 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 G protein-coupled receptor (GPCR) and G protein modulation of presynaptic calcium channels. We are currently investigating the molecular determinants of G protein inhibition of calcium channels and modulation of receptors and ion channels in inhibitory synaptic transmission in the mammalian cerebellum, recently extending this work to excitatory transmission in hippocampal brain slices. Our current focus here is on cannabinoid receptors, which we are investigating using electrophysiological recordings from brain slices. In addition, we have established tissue culture facilities to investigate GPCR and ion channel modulation in native neurones and recombinant cells.

Present research interests:

• Molecular determinants for G protein inhibition of calcium channels. Wellcome Trust- funded project grant (with Prof. Sumiko Mochida, Tokyo Medical University)
• Functional effects of CACHD1 on calcium channel function (BBSRC DTG (CASE award from Pfizer UK) PhD project with Dr Edward Stevens, Pfizer UK)
• SUMOylation of calcium channels (University of Reading funded PhD project with Dr Helena Cimarosti, University of Reading)
• Role of cannabinoids in hyperexcitability in the CNS (GW Pharmaceutics funded PDRA and PhDs (project with Dr Claire Williams and Dr Ben Whalley, University of Reading)
• Mechanism of action of the anti-convulsant levetiracetam (UCB Pharma funded PhD project with Dr Ben Whalley, University of Reading)
• Modulation of inhibitory neurotransmission in the cerebellum by cannabinoids (Ataxia UK funded PhD project with Dr Ben Whalley)
• Cannabinoid CB1 receptor signalling in the CNS (PhD project with Dr Ben Whalley, School of Pharmacy, University of Reading)

Research groups / Centres:

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

Publications:

Y

Jump to: 2013 | 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005

Number of items: 24.

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. ISSN 1469-7793 doi: 10.1113/jphysiol.2012.244947 (In Press)
• 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: 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: 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: 10.1111/j.1476-5381.2012.02207.x
• Jones, N. A., Glyn, S., Akiyama, S., Hill, T. D.M., Hill, A., Weston, S., Burnett, M. D.A., Yamasaki, Y., Stephens, G., Whalley, B. and Williams, C. (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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 10.1038/bjp.2008.190
• Ma, Y. L., Weston, S. E., Whalley, B. J. and Stephens, G. J. (2008) The phytocannabinoid Delta(9)-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum. British Journal of Pharmacology, 154 (1). pp. 204-215. ISSN 0007-1188 doi: 10.1038/bjp.2008.57
• 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: 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: 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: 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: 10.1113/jphysiol.2004.080192

This list was generated on Tue Jun 18 10:04:01 2013 BST.

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