Dr Noel Davies

Personal Details

Associate Professor

DepartmentMolecular and Cell Biology
Telephone:  0116 229 7138       
Emailnwd@le.ac.uk
Address: University Rd, Leicester, LE1 7RH
Web Links: 

Biography

My main interests have always been in the physiology and biophysics of ion channels. Following my PhD at the University of St Andrews I was awarded a Royal Society European Exchange Fellowship to work with Prof HD Lux on neuronal Ca2+ channels at the Max-Planck-Institute für Psychiatrie in Munich. After 2 years in Munich I came to the University of Leicester as a post-doctoral associate with Profs Peter Stanfield and Nick Standen to work on K+ channels in muscle. In 1991 I was awarded a Royal Society University Research Fellowship; after 8 years I was appointed a lecturer in the then Department of Cell Physiology and Pharmacology and in 2004 I was promoted to a Senior Lecturer (now Associate Professor).

Qualifications

  • BSc in Physiology, University of Wales (Cardiff)
  • PhD in Neurophysiology, University of St Andrews
  • Senior Fellow of the Higher Education Academy

Teaching

The topics I teach currently include membrane potentials and action potentials, cardiac physiology and pharmacology, liver function and disease, ion channel physiology and biophysics

Publications

  1. Kapetanaki, SM, Burton, MJ, Basran, J, Uragami, C, Moody, PCE, Mitcheson, JS, Schmid, R, Davies, NW, Dorlet, P, Vos, MH, Storey, NM & Raven, E (2018). A mechanism for CO regulation of ion channels Nature Comm 9:907-917.
  2. Lörinczi, E, Helliwell, M, Finch, A, Stansfeld, PJ, Davies, NW, Mahaut-Smith, MP, Muskett, F & Mitcheson, JS (2016) Calmodulin regulates hEAG1 channels through interactions of the eag-domain with the cyclic nucleotide binding homology domain. J Biol Chem 291(34):17907-17918.
  3. Burton, MJ, Kapetanaki, SM, Chernova, T, Jamieson, AG, Dorlet, P, Santolini, J, Moody, PCE, Mitcheson, JS, Davies, NW, Schmid, R, Raven, EL and Storey, NM (2016). A heme- binding domain controls regulation of ATP-dependent potassium channels. PNAS 113(14): 3785–3790
  4. Panhwar, F, Rainbow, RD, Jackson, R & Davies, NW (2015). Ca2+ dependent but PKC independent signalling mediates UTP induced contraction of rat mesenteric arteries. J Smooth Musc Res. 51:58-69.
  5. Brignell JL, Perry, MD, Nelson, CP, Willets, JM, Challiss, RAJ & Davies, NW (2015). Steady- state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B. PLOS ONE
  6. Nelson CP, Rainbow RD, Brignell JL, Perry MD, Willets JM, Davies NW, Standen NB & Challiss RA. (2011). Principal role of adenylyl cyclase 6 in K+ channel regulation and vasodilator signalling in vascular smooth muscle cells. Cardiovasc Res. 91:694-702.
  7. Rainbow, R.D., Parker, A.M. & Davies, N.W. (2011). Protein kinase C-independent inhibition of arterial smooth muscle K+ channels by a diacylglycerol analogue. Brit. J. Pharmacol. 163:845-856.
  8. Rainbow, R.D., Norman, R.I., Everitt, D.E., Brignell, J.L., Davies, N.W. & Standen, N.B. (2009). Endothelin I and angiotensin II inhibit arterial voltage-gated K+ channels through different PKC isoenzymes. Cardiovascular Research 83:493-500.
  9. Hamann M, Gibson A, Davies N, Jowett A, Walhin JP, Partington L, Affleck K, Trezise D & Main M. (2009). Human ClCa1 modulates anionic conduction of calcium-dependent chloride currents. J Physiol 587(10), 2255-2274.
  10. Nelson, CP, Willets, JM, Davies, NW, Challiss, RAJ, & Standen, NB (2008). Visualizing the temporal effects of vasoconstrictors on PKC translocation and Ca2+ signaling in single resistance arterial smooth muscle cells. American Journal of Physiology - Cell Physiology 295:C1590-1601.
  11. Hayabuchi, Y., Willars, G.B., Standen, N.B. & Davies, N.W. (2008). Insulin-like growth factor-I inhibits rat arterial KATP channels through PI 3-kinase. Biochemical and Biophysical Research Communications 374:742-746.
  12. El-Rachkidy, R.G., Davies, N.W. & Andrew, P.W. (2008). Pneumolysin generates multiple conductance pores in the membrane of nucleated cells. Biochemical and Biophysical Research Communications 368:786-792.
  13. Rainbow, R.D., Hardy, M.E.L., Standen, N.B. & Davies, N.W. (2006). Glucose reduces endothelin inhibition of voltage-gated potassium channels in rat arterial smooth muscle cells. Journal of Physiology 575(3): 833-844.
  14. Rainbow, R.D., Norman, R.I., Hudman, D., Davies, N.W. and Standen, N.B. (2005). Reduced effectiveness of HMR 1098 in blocking cardiac sarcolemmal KATP channels during metabolic stress. Journal of Molecular and Cellular Cardiology 39(4):637-646.
  15. Rainbow, R.D., Lodwick, D., Hudman, D., Davies, N.W., Norman, R.I. and Standen, N.B. (2004). SUR2A C-terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes. Journal of Physiology 577(3): 785-794.
  16. Rainbow, R.D., James, M., Hudman, D., Al Johi, M., Singh, H., Watson, P.J., Ashmole, I., Davies, N.W., Lodwick, D. and Norman, R.I. (2004). Proximal C-terminal domain of sulphonylurea receptor 2A interacts with pore-forming Kir6 subunits in KATP channels. Biochemical Journal 379(1):173-81.
  17. Rodrigo, G.C., Davies, N.W. & Standen, N.B. (2004). Diazoxide causes early activation of cardiac sarcolemmal KATP channels during metabolic inhibition by an indirect mechanism. Cardiovascular Research 61/3: 570-579
  18. Lippiat, J.D., Standen, N.B., Harrow, I.D., Phillips, S.C. & Davies, N.W. (2003). Properties of BKCa channels formed by bicistronic expression of hSloa and b1-4 subunits in HEK293 cells. Journal of Membrane Biology 192: 141-148.
  19. Lawrence, C.L, Rainbow, R.D., Davies, N.W. & Standen, N.B. (2002). Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal KATP channels. British Journal of Pharmacology 136(5): 746-752.
  20. Hayabuchi, Y., Standen, N.B. & Davies, N.W. (2001). Angiotensin II inhibits and alters kinetics of voltage gated K+ channels of rat arterial smooth muscle. American Journal of Physiology 281: H2480-H2489.
  21. Lewis, C.J., Davies, N.W. & Evans, R.J. (2001). Permeability and single channel properties of mesenteric, basilar and septal (coronary) artery smooth muscle P2X receptors. Drug Development Research 52: 164-169.
  22. So, I., Ashmole, I., Davies, N.W., Sutcliffe, M.J. & Stanfield, P.R. (2001). The K+ channels signature sequence of murine Kir2.1: mutations that affect microscopic gating but not ionic selectivity. Journal of Physiology 531(1): 37-49.
  23. Hayabuchi, Y., Davies, N.W. & Standen, N.B. (2001). Angiotensin II inhibits rat arterial KATP channels by inhibiting steady-state PKA activity and activating PKCε. Journal of Physiology 530(2):193-205.
  24. Lippiat, J.D., Standen, N.B. & Davies, N.W. (2000). A residue in the intracellular vestibule of the pore is critical for gating and permeation in Ca2+-activated K+ (BKCa) channels. Journal of Physiology 529(1):131-138.
  25. Kamishima, T., Davies, N.W. & Standen, N.B. (2000). Mechanisms that regulate [Ca2+]i following depolarization in rat systemic arterial smooth muscle cells. Journal of Physiology 522: 285-295.
  26. Lippiat, J.D., Standen, N.B. & Davies, N.W. (1998). Block of cloned BKCa channels (rSlo) expressed in HEK 293 cells by N-methyl D-glucamine. Pflügers Archiv 436:810-812.
  27. Barrett-Jolley, R., & Davies, N. W. (1997). Kinetic analysis of the inhibitory effect of glibenclamide on KATP channels of mammalian skeletal muscle. Journal of Membrane Biology 155(3): 257-262.
  28. Abrams, C.J., Davies, N.W., Shelton, P.A., & Stanfield, P.R. (1996). The role of a single aspartate residue in ionic selectivity and block of a murine inward rectifier K+ channel Kir2.1. Journal of Physiology 493(3): 643-649.
  29. Barrett-Jolley, R., Comtois, A., Davies, N. W., Stanfield, P. R., & Standen, N. B. (1996). Effect of adenosine and intracellular GTP on KATP channels of mammalian skeletal muscle. Journal of Membrane Biology 152(2):111-116.
  30. Davies, N.W., McKillen, H.-C., Stanfield, P.R. & Standen, N.B. (1996). A rate theory model for Mg2+ block of ATP-dependent potassium channels of rat skeletal muscle. Journal of Physiology 490(3): 817-826.
  31. McKillen, H.-C., Davies, N.W., Standen, N.B. & Stanfield, P.R. (1994). The effect of intracellular anions on ATP-dependent potassium channels of rat skeletal muscle. Journal of Physiology 479:341-351.
  32. Stanfield, P.R., Davies, N.W., Shelton, P.A., Sutcliffe, M.J., Khan, I.A., Brammar, W.J. & Conley, E.C. (1994). A single aspartate residue is involved in both intrinsic gating and blockage by Mg2+ of the inward rectifier, IRK1. Journal of Physiology 478:1-6.
  33. Shen, K.-Z., Lagrutta, A., Davies, N.W., Standen, N.B., Adelman, J.P. & North, R.A. (1994). Tetraethylammonium block of Slowpoke calcium-activated potassium channels expressed in Xenopus oocytes: evidence for tetrameric channel formation. Pflügers Archiv. 426:440-445.
  34. Stanfield, P.R., Davies, N.W., Shelton, P.A., Khan, I.A. Brammar, W.J., Standen, N.B. & Conley, E.C. (1994). The intrinsic gating of inward rectifier K+ channels expressed from the murine IRK1 gene depends on voltage, K+ and Mg2+. Journal of Physiology 475:1-7.
  35. Beirão, P.S.L., Davies, N.W. & Stanfield, P.R. (1994). Inactivating 'ball' peptide from Shaker B blocks Ca2+-activated but not ATP-dependent K+ channels of rat skeletal muscle. Journal of Physiology 474:269-274.
  36. Shelton, P.A., Davies, N.W., Antoniou, M., Grosveld, F., Needham, M., Hollis, M., Brammar, W.J. & Conley, E.C. (1993). Regulated expression of K+ channel genes in electrically silent mammalian cells by linkage to β-globin gene-activation elements. Receptors and Channels 1:25-37.
  37. Standen, N.B., Pettit, A.I., Davies, N.W. & Stanfield, P.R. (1992). Activation of ATP-dependent K+ currents in intact skeletal muscle fibres by reduced intracellular pH. Proceedings of the Royal Society B 247:195-198.
  38. Davies, N.W., Standen, N.B. & Stanfield, P.R. (1992). The effect of intracellular pH on ATP-dependent potassium channels of frog skeletal muscle. Journal of Physiology 445:549-568
  39. Davies, N.W., Pettit, A.I., Agarwal, R. & Standen, N.B. (1991). The flickery block of ATP-dependent potassium channels of skeletal muscle by internal 4-aminopyridine. Pflügers Archiv. 419:25-31.
  40. Davies, N.W., Standen, N.B. & Stanfield, P.R. (1991). ATP-dependent potassium channels of muscle cells: Their properties, regulation, and possible functions. Journal of Bioenergetics and Biomembranes 23:509-535.
  41. Cottrell, G.A., Green, K.A. & Davies, N.W. (1990). The neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) can activate a ligand-gated ion channel in Helix neurones. Pflügers Archiv. 416:612-614.
  42. Davies, N.W. (1990). Modulation of ATP-sensitive K+ channels in skeletal muscle by intracellular protons. Nature 343:357-377.
  43. Standen, N.B., Quayle, J.M., Davies, N.W., Brayden, E., Huang, Y. & Nelson, M. (1989). Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science 245:177-180.
  44. Davies, N.W., Spruce, A.E., Standen, N.B. & Stanfield, P.R. (1989). Multiple blocking mechanisms of ATP-sensitive potassium channels of frog skeletal muscle by tetraethylammonium ions. Journal of Physiology 413:31-48.
  45. Morad, M., Davies, N.W., Ulrich, G. & Schultheiss, H-P. (1988). Antibodies against ADP/ATP carrier enhance the calcium current in isolated cardiac myocytes. American Journal of Physiology 255:H960-H964.
  46. Morad, M., Davies, N.W., Kaplan, J.H. & Lux, H.D. (1988). Photo-release of Ca2+ in dorsal root ganglion neurones shows that Ca2+-induced inactivation of Ca2+ channel depends on the permeant cation. Science 241:842-844.
  47. Davies, N.W., Lux, H.D. & Morad, M. (1988). Site and mechanism of activation of proton-induced sodium current in chick dorsal root ganglion neurones. Journal of Physiology 400:159-187.
  48. Price, D.A., Davies, N.W., Doble, K. & Greenberg, M.J. (1987). The variety and distribution of the FMRFamide-related peptides in molluscs. Zoological Sciences. 4:395-410.
  49. Cottrell, G.A., Bewick, G. & Davies, N.W. (1987). Multiple receptors of the FMRFamide series of intercellular messengers. In: Neurobiology, Molluscan Models. Eds. H.H. Boer, W.P.M. Geracks & J. Joose. pp 115-123. North Holland, Amsterdam.
  50. Cottrell, G.A. & Davies, N.W. (1987). Multiple receptor sites for molluscan peptide (FMRFamide) and related peptides of Helix. Journal of Physiology 382:51-68.
  51. Cottrell, G.A., Davies, N.W. & Green, G.A. (1984). Multiple actions of molluscan cardioexcitatory neuropeptide and related peptides on identified Helix neurones. Journal of Physiology 356:315-333.

Research

My main research focuses on two areas:

  1. The physiology and biophysics of K+ channels and in particular on their regulation by haem-dependent processes. This work involves structure/function studies of haem interaction with K+ channels and an investigation of haem-dependent regulation in arterial smooth muscle.
  2. The regulation of cardiac Ca2+ currents by nitric oxide. This involves examining the different signalling pathways whereby NO can modulate cardiac Ca2+ current. These experiments used the perforated single-electrode voltage-clamp technique.

Both of these projects involve detailed analysis of electrophysiological data which are obtained using single-channel, whole-cell patch-clamp and single-electrode voltage-clamp recording. I also develop analysis software and am interested in modelling electrophysiological data.

Techniques

  • Whole-cell recording of K+ currents from native cells and mammalian cell-lines
  • Single channel recording of K+ channels
  • Voltage-clamp recording of cardiac Ca2+ currents
  • Development of analysis software for electrophysiological data
  • Kinetic modelling of electrophysiological data

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Department of Molecular and Cell Biology

T: +44(0)116 229 7038
E: MolCellBiol@le.ac.uk

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