Dr Catherine Vial

Research Interests and Techniques

Extracellular nucleotides act on plasma membrane P2 receptors to mediate numerous physiological responses including regulation of vascular tone and platelet aggregation. P2 receptors are well represented in the circulatory system and are found on smooth muscle, endothelium, in the heart and haematic cells. P2 receptors are composed of two subfamilies: seven ionotropic P2X receptors (P2X1-7) and eight metabotropic P2Y receptors (P2Y1,2,4,6,11-14).

Our research has focused on the study of P2 receptors in the circulatory system (arteries and haematic cells). We have participated to the identification and characterisation the P2X and P2Y receptors expressed on human platelets and shown their involvement in platelet aggregation, demonstrated the functional role of homomeric P2X1 receptors in smooth muscle (bladder, the renal system, male reproductive organs, gut) and in blood cells (platelets and megakaryocytes). We have also investigated the contribution of P2X1 and different subtypes of P2Y receptors in smooth muscle contraction and in thrombosis, showing the important role of P2 receptors in circulatory system.

More recently, we have been interested in the characterisation and the study of the functional roles of P2 receptors in mast cells. Mast cells contribute to the development of cardiovascular diseases such as thrombosis and atherosclerosis, nevertheless the mechanisms involved remain unclear. P2 receptors for nucleotides are possible candidates since P2 receptors are expressed on mast cells and ATP has been shown to induce histamine secretion, chemotaxis, cytokine generation and apoptosis in mast cells. Moreover, P2 receptors are known to play a key role in haemostasis. We now intend to identify and characterise the functional P2 receptors present on mast cells and to determine their contribution to mast cell antithrombotic and proangiogenic activity.

Techniques

Methods currently used in our laboratory include:

• Patch clamp recording of currents flowing through ion channels from whole cells
• Recombinant approaches to generate molecular constructs for the manipulation of channels and signalling pathways in native cells: dominant negatives, overexpression, RNA interference
• Fluorescent measurements of intracellular [Ca2+]
• Imaging methods to detect location and movement of EGFP-tagged proteins
• Molecular biology (RT-PCR, qPCR, cloning…)
• Biochemistry (Western Blotting, immunoprecipitation…)
• ELISA
• Cell culture (various primary cells and cell lines)

Research Group Funding

The British Heart Foundation

Selected Publications

Wareham K, Vial C, Wykes R, Bradding P & Seward E (2009) Functional evidence for the expression of P2X1, P2X4 and P2X7 receptors in human lung mast cells. Br J Pharmacol. 157, 1215-1224.

Fryatt A.G, Vial C, Mulheran M, Gunthorpe M & Grubb B.D (2009) Voltage-Gated Sodium Channel Expression in Rat Spiral Ganglion Neurons. Mol Cell Neurosci. Dec;42(4):399-407.

Heppner YJ, Werner ME, Nausch B, Vial C, Evans RJ & Nelson MT (2009) Nerve-evoked purinergic signalling suppresses action potentials, Ca2+ flashes and contractility evoked by muscarinic receptor activation in mouse urinary bladder smooth muscle. J Physiol. 587(21), 5275-5288.

Harrington LS, Evans RJ, Wray JA, Norling LV, Swales KE, Vial C, Ali F, Carrier MJ and Mitchell JA. (2007) P2X1 receptors mediate endothelial dependent vasodilatation to ATP. Mol Pharmacol. 72(5):1132-6.

Lamont C, Vial C, Evans RJ and Wier WG. (2006) P2X1 receptors mediate sympathetic post-junctional Ca2+ transients (jCaTs) in mesenteric small arteries. Am J Physiol Heart Circ Physiol. 291, H3106-H3113.

Vial C, Fung CYE, Goodall AH, Mahaut-Smith MP and Evans RJ. (2006) Differential sensitivity of human platelet P2X1 and P2Y1 receptors to disruption of lipid rafts. Biochem. Biophys. Res. Comm. 343(2), 415-419.

Vial C and Evans RJ. (2005) Disruption of Lipid rafts inhibits P2X1 receptor-mediated currents and arterial vasoconstriction. J. Biol. Chem. 280(35), 30705-30711.

Tolhurst G, Vial C, Leon C, Gachet C, Evans RJ and Mahaut-Smith MP. (2005) Interplay between P2Y1, P2Y12 and P2X1 receptors in the activation of megakaryocyte cation influx currents by ADP; evidence that the primary megakaryocyte represents a fully functional model of platelet P2 receptor signaling. Blood. 106(5), 1644-1651.

Martinez-Pinna J, Gurung IS, Vial C, Leon C, Gachet C, Evans RJ and Mahaut-Smith MP. (2005) Direct voltage control of signaling via P2Y1 and other G q-coupled receptors. J. Biol. Chem. 280(2), 1490-1498.

Vial C, Roberts JA and Evans RJ. (2004) Molecular properties of ATP-gated P2X receptor ion channels. Trends in Pharmacol. Sci. 25 (9), 487-493.

Vial C, Tobin AB and Evans RJ. (2004) G-protein coupled receptor regulation of P2X1 receptors does not involve direct channel phosphorylation. Biochem J. 382 (Pt 1), 101-110.

Vial C, Pitt SJ, Roberts J, Rolf MG, Mahaut-Smith MP and Evans RJ. (2003) Lack of evidence for functional ADP-activated human P2X1 receptors supports a role for ATP during hemostasis and thrombosis. Blood. 102, 3646-51.

Hechler B, Lenain N, Marchese P, Vial C, Heim V, Freund M, Cazenave JP, Cattaneo M, Ruggeri ZM, Evans R and Gachet C. (2003) A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo. J Exp Med. 198, 661-7.

Vial C and Evans RJ. (2002) P2X(1) Receptor-Deficient Mice Establish the Native P2X Receptor and a P2Y(6)-Like Receptor in Arteries. (2002) Mol Pharmacol. 62(6):1438-1445.

Vial C, Rolf MG, Mahaut-Smith MP and Evans RJ. (2002) A study of P2X(1) receptor function in murine megakaryocytes and human platelets reveals synergy with P2Y receptors. Br J Pharmacol. 135(2):363-372.

Vial C and Evans RJ. (2001) Smooth muscles does not have a common P2x receptor phenotype: expression, ontogeny and function of P2x1 receptors in mouse ileum, bladder and reproductive systems.Auton Neurosci. 92(1-2):56-64.