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Title: P2X receptor function in an extreme ionic environment
Author: Goodey, G. C.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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ATP activates P2X receptors in the apical surface of kidney epithelial cells. However, tubular fluid is unusual - with low sodium levels, high calcium levels and acidic in nature. This study investigated how P2X receptors operate in extreme ionic environments. Xenopus oocytes easily tolerated extreme ionic environments. Their membrane properties and pharmacological profile were examined under normal and extreme ionic conditions. It was confirmed that oocytes lack endogenous P2X receptors, and were unaffected by P2X receptor antagonists and allosteric modulators. Also, oocytes lacked muscarinic receptors. The pharmacological profile of P2X2 and P2X4 receptors expressed in oocytes were examined under normal and extreme ionic conditions. Each P2X subtype was activated by ATP and CTP and this activity was affected by extracellular ions. At rat P2X2, reduced extracellular sodium had an inhibitory effect on ATP signalling, which was reversed by acidifying of the medium or intensified by adding calcium to the medium. At rat P2X4, reduced extracellular sodium had a biphasic action (potentiation, then inhibition) on ATP signalling, which was insensitive to acidification but was intensified by adding calcium. A unique electrophysiological property of P2X2-expressing oocytes was used to investigate an ATP-releasing mechanism. An inward current (Ix) was identified and this current was blocked by the P2 receptor antagonist, suramin, and inhibited by the ATP-degrading enzyme, apyrase. The amplitude of IX was affected by the flow rate of the superfusate, confirming that ATP was released by a mechanosensory process. The present results show that ATP may activate P2X receptors present in the kidney, even in the extreme ionic environment of the distal nephron. Salt and water reclamation in the kidney may depend on flow rate, since a common mechanosensory mechanism can release enough ATP to activate those P2X receptors regulating ENaC and AQP2 channel function in the distal nephron.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available