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Title: The P2X receptor mediated regulation of inhibitory synaptic transmission
Author: Andrew-Adiamah, Jemma
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2012
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In the central nervous system ATP can be released by neurons and glial cells through similar pathways as other neurotransmitters. Extracellular ATP targets P2X purinoreceptors, causing an influx of Ca2+ ions which transmit very important messages for neurons and glial cells. Ionic signals modulated by P2X receptors can be transformed into the modulation of GABAA receptors. This work describes the universal interaction of P2X receptors downregulating GABAA mediated currents via a Ca2+-dependent mechanism. I have shown that the postsynaptic modulation of GABA currents by P2X receptors is present in both the peripheral (DRG neurons) and central nervous system (cortical neurons). This effect is strongly regulated by an intracellular signalling cascade involving Protein Kinase C. Furthermore, tonically-activated GABAA receptors expressed on central neurons, containing alpha5 and delta subunits are also affected by this P2X and GABAA receptor interaction. The purinergic modulation of GABAA receptors has significant implications for synaptic plasticity, an important mechanism of learning and memory in the central nervous system. The down-regulation of GABAA receptors on the postsynaptic membrane enhances the activity of NMDA receptors and thus increases synaptic efficacy. The study of the purinergic involvement in the induction of Long Term Potention is far from being understood. Ionotrophic purinoceptors represent a novel pathway of GABAA receptor modulation: release of ATP from neurons and astrocytes activates Ca2+- signalling via purinergic P2X receptors, which can regulate GABAA receptors activity in both peripheral and central nervous system compartments. The physiological implications of this regulatory pathway are yet to be investigated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology