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Renal transport proteins
The activity of a number of transport proteins in the nephron are modified by the tubular perfusion of adenosine 5'-triphosphate (ATP) even though they themselves are insensitive to extracellular ATP. Thus, activation of an abundance of cell-surface ATP-gated receptors, known as P2 receptors, by endogenous ATP (secreted from cells as an autocrine or paracrine factor) has been proposed to indirectly regulate renal solute and water transporter activity. In my laboratory, I investigate interactions between ATP-gated receptors (P2 receptors) and renal transport proteins using two experimental approaches. Firstly, I explore the molecular mechanisms of receptor/channel interactions in isolation in the Xenopus oocyte expression system by co-expressing transport proteins and P2 receptors (based on RT-PCR and immunohistochemical data), using twin-electrode electrophysiology. Secondly, I investigate transport activity in response to extracellular ATP in the apical membrane of intact cells of the rat collecting duct (CD), using the microdissected isolated split-open tubule technique and patch clamp electrophysiology. I have international collaborations with groups in New York (USA), Lausanne (Switzerland) and Nijmegen (The Netherlands).
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