Tlie long term goal of this study is to elucidate tfie molecular mechanisms underlying P2X receptor functions by combining structural and functional approaches. P2X receptors are trimeric ATP-gated ion channels that are widely distributed throughout the human body. Activation of these receptors causes cation influx that evokes action potentials or triggers calcium mediated signaling, important functions in signal transmission, inflammation, and pain sensation. While the first crystal structure in its closed state provides a number of novel insights into receptor architecture, mechanisms of P2X receptor functions are largely unknown. To determine the cation selection mechanism and the structural changes during gating, two specific aims are designed as follows;1) to identify the ion selection machinery using patch clamp recording techniques, and 2) to localize ion binding sites and determine the crystal structure in the open state using X-ray crystallography. Completion of these studies is expected to provide the first compelling mechanisms and structural basis for the cation selectivity, which may in turn lead to the design of novel pharmacological agents targeting P2X receptors.

Public Health Relevance

;. P2X receptors are ion channels widely distributed throughout the human body and play important roles in inflammatory response and pain sensation. My research objective is to understand meehahisrris of how P2X receptors function at a mdlecular level, which may lead to the design of novel pharmacological agents to treat inflammatory diseases and to relieve pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Transition Award (R00)
Project #
5R00NS072869-04
Application #
8514088
Study Section
Special Emphasis Panel (NSS)
Program Officer
Stewart, Randall R
Project Start
2011-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$233,223
Indirect Cost
$75,589
Name
Cornell University
Department
Other Basic Sciences
Type
Schools of Veterinary Medicine
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850