Research Interests and Techniques

My current research is focused on the physiology and biophysics of the K+ channels of arterial smooth muscle and on their regulation by vasoactive compounds. K+ channels have a wide range of physiological roles and to accomplish this they have widely varying properties. At least 4 different types of K+ channels exist in arterial smooth muscle (Kv, BKCa, KATP and Kv channels) and their regulation is partly dependent on the activity of PKA and PKC. These projects involve detailed analysis of electrophysiological data which are obtained using single-channel and whole-cell patch-clamp recording. I also develop analysis software and am interested in modelling electrophysiological data.

In addition to this, the role that these K+ channels play in regulating the diameter of arteries is investigated using myographical techniques, and real time imaging of tagged second messenger compounds is used to track signalling events in smooth muscle cells following application of vasoactive compounds.

Techniques

• Whole-cell recording from native cells and mammalian cell-lines - present emphasis on arterial smooth muscle cells
• Single channel recording of K+ channels imaging techniques
• Development of analysis software for electrophysiological data
• Kinetic modelling of electrophysiological data

Research Group and Funding

Present group members

Dr Jenny Brignell
Dr Carl Nelson

Current funding

British Heart Foundation

Islamic Development Bank (Fouzia Panhwar)

Recent Publications

Rainbow RD, Norman RI, Everitt DE, Brignell JL, Davies NW and Standen NB. (2009). Endothelin I and angiotensin II inhibit arterial voltage-gated K+ channels through different PKC isoenzymes. Cardiovascular Research 83:493-500.

Nelson CP, Willets JM, Davies NW, Challiss RAJ and Standen NB. (2008). Visualizing the temporal effects of vascoconstrictors on PKC translocation and Ca2+ signaling in single resistance arterial smooth muscle cells. American Journal of Physiology - Cell Physiology 295:C1590-1601.

Hayabuchi Y, Willars GB, Standen NB and Davies NW. (2008). Insulin-like growth factor-I inhibits rat arterial KATP channels through PI 3-kinase. Biochemical and Biophysical Research Communications 374:742-746.

El-Rachkidy RG, Davies NW and Andrew PW. (2008). Pneumolysin generates multiple conductance pores in the membrane of nucleated cells. Biochemical and Biophysical Research Communications 368:786-792

Rainbow RD, Hardy MEL, Standen NB and Davies NW. (2006). Glucose reduces endothelin inhibition of voltage-gated potassium channels in rat arterial smooth muscle cells. Journal of Physiology 575(3): 833-844.

Rainbow RD, Norman RI, Hudman D, Davies NW and Standen NB (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

Rainbow RD, Lodwick D, Hudman D, Davies NW, Norman RI and Standen NB. (2004). SUR2A C-terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes. Journal of Physiology 577(3): 785-794.

Rainbow RD, James M, Hudman D, Al Johi M, Singh H, Watson PJ, Ashmole I, Davies NW, Lodwick D and Norman RI. (2004). Proximal C-terminal domain of sulphonylurea receptor 2A interacts with pore-forming Kir6 subunits in KATP channels. Biochemical Journal 379(1):173-81.

Rodrigo GC, Davies NW and 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.

Lippiat JD, Standen NB and Davies NW. (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.

Lawrence CL, Rainbow RD, Davies NW and Standen NB. (2002). Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal KATP channels. British Journal of Pharmacology 136: 746-752.

Hayabuchi Y, Standen NB and Davies NW. (2001). Angiotensin II inhibits and alters kinetics of voltage gated K+ channels of rat arterial smooth muscle. American Journal of Physiology 281:H2480-H2489.

Hayabuchi Y, Davies NW and Standen NB. (2001). Angiotensin II inhibits rat arterial KATP channels by inhibiting steady-state PKA activity and activating PKCe. Journal of Physiology 530(2),193-205.

So I, Ashmole I, Davies NW, Sutcliffe MJ and Stanfield PR. (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.

Lewis CJ, Davies NW and Evans RJ. (2001). Permeability and single channel properties of mesenteric, basilar and septal (coronary) artery smooth muscle P2X receptors. Drug Development Research 52: 164-169.

Lippiat JD, Standen NB and Davies NW. (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, 131-138.

Kamishima T, Davies NW and Standen NB. (2000). Mechanisms that regulate [Ca2+]i following depolarization in rat systemic arterial smooth muscle cells. Journal of Physiology 522, 285-295.

Lippiat JD, Standen NB and Davies NW. (1998). Block of cloned BK(Ca) channels (rSlo) expressed in HEK 293 cells by N-methyl D-glucamine. (1998) Pflügers Archiv 436(5): 810-812.

Barrett-Jolley R and Davies NW. (1997). Kinetic analysis of the inhibitory effect of glibenclamide on KATP channels of mammalian skeletal muscle. Journal of Membrane Biology, 155(3), 257-262.

Davies NW, McKillen HC, Stanfield PR and Standen NB. (1996). A rate theory model for Mg2+ block of ATP-dependent potassium channels of rat skeletal muscle. Journal of Physiology, 490(3), 817-826.

Abrams CJ, Davies NW, Shelton PA and Stanfield PR. (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.