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Gary Stephens

Gary Stephens

Director of Pharmacology

Areas of interest

  • Functional effects of CACHD1 on calcium channels
  • SUMOylation of calcium channels (with Dr Helena Cimarosti, Universidade Federal de Santa Catarina (UFSC), Brazil and Prof Sumiko Mochida, Tokyo Medical University, Japan)
  • Modulation of calcium channels by Abeta peptide and effects of carbon monoxide (Alzheimer's Association-funded project with Mark Dallas, University of Reading)
  • Role of plant cannabinoids in hyperexcitability in the CNS
  • Modulation of inhibitory neurotransmission in the cerebellum

Research centres and groups

Memberships:

  • Co-Chair British Pharmacological Society Molecular & Cellular Pharmacology Affinity Group
  • British Journal of Pharmacology Editorial Board: Senior Editor
  • Fellow of British Pharmacological Society
  • Fellow of The Physiological Society
  • The Calcium Channel Network
  • Pharmaceuticals Editorial Board
  • School of Pharmacy, Pharmacology Group
  • Electrophysiology and Behavioural Neuroscience Group
  • Centre for Neuroscience and Neurodynamics

Background

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 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.

Selected publications

Other Publications

Harvey, V.L & Stephens, G.J. (2004) Mechanism of GABAB 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 CaV2.1/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

Publications