Research summary

Dr Kim Dora

Dr Dora's research focuses on cell-cell communication in resistance arteries and arterioles. Predominantly focussing on signalling pathways within the endothelium, she uses sophisticated and novel techniques to monitor rapid changes in intracellular Ca²⁺ and how they link to the activation of dilator pathways. Her work has shown that  gap junctions between endothelial and smooth muscle cells enable the spread of current and Ca²⁺ signals between the cell types, and as a result, control arterial diameter. How these signals are generated and modulated is of ongoing interest.

Spontaneous vasomotion, followed by dilatation to 1 µM ACh in an isolated, triple cannulated and pressurized arteriole. Feed arteriole ~1000 µm long.

Dr Dora’s research is currently focussed on 5 main research areas 1) intra- and inter-cellular Ca²⁺ imaging in isolated pressurized small arteries and arterioles, 2) endothelium-dependent control of arterial diameter, 3) electrical events leading to conducted dilatation, 4) lumen-specific actions of agonists and 5) how these processes are affected by endothelial dysfunction.

Spontaneous and agonist-mediated endothelial cell Ca2+ events in an isolated pressurized arteriole. An agonist acting at endothelial cell muscarinic receptors was added t=6 s. Movie 10x real time, frame width 250 µm.

Dr Dora obtained a BSc (Biochemistry) at the Australian National University and a PhD with Professor Michael Clark in Biochemistry from the University of Tasmania. She was then awarded a CJ Martin Overseas Research Fellowship (from the NH&MRC Australia) to work with Dr Brian Duling in the Department of Physiology and Biological Physics at the University of Virginia, USA. In 1997 she moved to the UK to the Department of Pharmacology at the University of Bristol to work with Professor Chris Garland. She became a Lecturer at the University of Bath in 2000, where she became Senior Lecturer and then Reader in Vascular Pharmacology. In 2008 she was awarded a BHF Senior Basic Science Research Fellowship and moved to Pharmacology in Oxford in October.

Dr Dora is on the Council of the British Pharmacological Society, and is an Editor for the British Journal of Pharmacology (2003-2009). She is the Endothelium SIG coordinator for the BPS.

Collaborators

• Prof Chris Garland, Professor of Vascular Pharmacology , University of Oxford
• Dr Pooneh Bagher, Postdoctoral Research Fellow , University of Oxford
• Dr Timea Beleznai, Postdoctoral Fellow , University of Oxford
• Dr Melike Ozkan, Visitor , Haccetepe Universite, Turkey
• Dr Claire Doyle, Postdoctoral Fellow , University of Oxford
• Harrison Davis, DPhil Student , University of Oxford
• Drew Duglan, DPhil Student , University of Oxford
• Chloe Lim, DPhil Student , University of Oxford
• Ray Mitchell, Imaging Data Analyzer , University of Oxford
• Dr Rosalia Rodriguez-Rodriguez
• Dr Polina Yarova

2013

Linking hyperpolarization to endothelial cell calcium events in arterioles.

Dora, KA and Garland, CJ
Microcirculation.

Measurement of changes in endothelial and smooth muscle Ca(2)(+) in pressurized arteries.

Dora, KA and Hill, MA
Methods Mol Biol, 937:229-38.

2012

Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca2+ events, and IKCa channels, reducing arteriolar tone.

Bagher, P, Beleznai, T, Kansui, Y, Mitchell, R, Garland, CJ, and Dora, KA
Proc Natl Acad Sci U S A.

2011

A novel role for HNO in local and spreading vasodilatation in rat mesenteric resistance arteries.

Yuill, KH, Yarova, P, Kemp-Harper, BK, Garland, CJ, and Dora, KA
Antioxid Redox Signal, 14(9):1625-35.

EDHF: spreading the influence of the endothelium.

Garland, CJ, Hiley, CR, and Dora, KA
Br J Pharmacol, 164(3):839-52.

Enhanced K(+)-channel-mediated endothelium-dependent local and conducted dilation of small mesenteric arteries from ApoE(-/-) mice.

Beleznai, T, Takano, H, Hamill, C, Yarova, P, Douglas, G, Channon, K, and Dora, K
Cardiovasc Res, 92(2):199-208.

Smooth muscle Ca(2+) -activated and voltage-gated K+ channels modulate conducted dilation in rat isolated small mesenteric arteries.

Beleznai, TZ, Yarova, PL, Yuill, KH, and Dora, KA
Microcirculation, 18(6):487-500.

Spatial distribution and mechanical function of elastin in resistance arteries: a role in bearing longitudinal stress.

Clifford, PS, Ella, SR, Stupica, AJ, Nourian, Z, Li, M, Martinez-Lemus, LA, Dora, KA, Yang, Y, Davis, MJ, Pohl, U, Meininger, GA, and Hill, MA
Arterioscler Thromb Vasc Biol, 31(12):2889-96.

Vascular hyperpolarization to beta-adrenoceptor agonists evokes spreading dilatation in rat isolated mesenteric arteries.

Garland, CJ, Yarova, PL, Jimenez-Altayo, F, and Dora, KA
Br J Pharmacol, 164(3):913-21.

2010

Coordination of vasomotor responses by the endothelium.

Dora, KA
Circ J, 74(2):226-32.

Development of an image-based system for measurement of membrane potential, intracellular Ca(2+) and contraction in arteriolar smooth muscle cells.

Ella, SR, Yang, Y, Clifford, PS, Gulia, J, Dora, KA, Meininger, GA, Davis, MJ, and Hill, MA
Microcirculation, 17(8):629-40.

Nitric oxide suppresses cerebral vasomotion by sGC-independent effects on ryanodine receptors and voltage-gated calcium channels.

Yuill, KH, McNeish, AJ, Kansui, Y, Garland, CJ, and Dora, KA
J Vasc Res, 47(2):93-107.

2008

Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries.

Kansui, Y, Garland, CJ, and Dora, KA
Cell Calcium, 44(2):135-46.

Evidence against C-type natriuretic peptide as an arterial 'EDHF'.

Garland, CJ and Dora, KA
Br J Pharmacol, 153(1):4-5.

Modulation of endothelial cell KCa3.1 channels during endothelium-derived hyperpolarizing factor signaling in mesenteric resistance arteries.

Dora, KA, Gallagher, NT, McNeish, A, and Garland, CJ
Circ Res, 102(10):1247-55.