MOLECULAR MECHANISMS REGULATING ATP SIGNALING IN MOUSE SENSORY NEURONSTanja Bele
, 2015, doctoral dissertation
Abstract: Coordinated and harmonized neuronal and glial responses to variations in extracellular levels of active soluble mediators such as ATP are essential in controlling neuronal activity. In pathological conditions involving sensory nervous system, elevations in extracellular ATP levels are believed to be one of the main reason for neuronal sensitization.
This notion led us to explore mechanisms of ATP release in sensory ganglia and we found that association among P2X purinergic receptors, their downstream effectors (CASK and CaMKII) and hemichannel Panx1 regulates inhibition of ATP release in basal conditions and that same players are involved in P2X3 receptor evoked-ATP release which globally suggest that even if observed proteins are expressed in different cells, they could be modulated by similar mechanisms and are possibly part of an “ATP-keeper molecular system” that finely regulates extracellular levels of ATP by its sensing and further adjustments of peculiar extracellular concentrations.
Further we showed that P2X3 receptors interact with Panx1 in sensory neurons and that molecular coupling between P2X3, CASK and Panx1 contributes to decoding of the complex purinergic signaling involved in nociception which represents a novel and interesting mechanism of pain regulation that could be precisely targeted in order to alleviate tedious disorders of sensory neurons.
Found in: ključnih besedah
Summary of found: ...among P2X purinergic receptors, their downstream effectors ( CASK and CaMKII) and hemichannel Panx1 regulates inhibition...
Keywords: ATP, ATP release, purinergic signaling, trigeminal ganglion, pain, migraine, P2X3, CASK, Pannexin-1, synaptic strength
Published: 10.12.2015; Views: 3732; Downloads: 182
Fulltext (3,75 MB)