Pannexin 1 Channel Regulation and Function, Relevance to Both Normal Physiology and Disease

Weaver, Janelle, Pharmacology - Graduate School of Arts and Sciences, University of Virginia
Bayliss, Douglas, Department of Pharmacology, University of Virginia
Leitinger, Norbert, Department of Pharmacology, University of Virginia
Beenhakker, Mark, Department of Pharmacology, University of Virginia
Guyenet, Patrice, Department of Pharmacology, University of Virginia
Ravichandran, Kodi, Department of Microbiology, University of Virginia

Pannexin 1 (Panx1) channels are widely expressed membrane proteins that are thought to mediate adenosine triphosphate (ATP) release from many cell types. Through this capability, Panx1 can perpetuate puringeric signaling events, which are crucial for intra and intercellular communication in many physiologic contexts. Despite interest in the channels, there are still many unknowns regarding Panx1 – specifically how is the channel activity regulated in vivo, and how and where do these channels have a physiologic or pathophysiologic role? In this dissertation, I present three sets of results that expand on these gaps in the current literature. First, I report on the identification of a novel post-translational modification of the channel. Next, I ask whether the channel has a role in neuropathic pain and expand on the mechanism of how Panx1 might contribute to this condition. Finally, I look at a daily, more physiologic role for Panx1. These three sections represent significant advances to the field of pannexin channels and introduce many new opportunities for future studies.

PHD (Doctor of Philosophy)
neuropathic pain, channel regulation, pannexin 1, S-Nitrosylation, spared nerve injury
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