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MODULATION OF THE TRANSIENT RECEPTOR "POTENTIAL ION CHANNEL MELASTATIN 3 (TRPM3) BY MEMBRANE PHOSPHOINOSITIDES AND HETEROMERIC G PROTEINS"

by
Doreen Badheka
Pharmacology and Physiology Program
B.S. 2005, St. Xavier’s College, Gujarat University, India
M.S. 2009, New York Medical College, NY


Thesis Advisor: Tibor Rohacs, MD, Ph.D.
Professor, Department of Pharmacology, Physiology and Neuroscience

Wednesday, May 11, 2016
1:00 P.M., MSB H609


Abstract

TRPM3 is the most recently identified thermosensitive TRP channel which is also important for nociceptive behavior. The functional importance of TRPM3 has been well-established through experiments in dorsal root ganglion neurons, trigeminal neurons and behavioral studies in knockout mice. However its basic regulation has yet to be explored. Since most members of the TRP ion channel family and many other families of ion channels are modulated by the membrane phosphoinositide phosphatidylinositol 4,5 bisphosphate ((PI(4,5)P2) we decided to test the role of this lipid in TRPM3 regulation. At the level of excised inside out patch clamp, two electrode voltage clamp and whole-cell patch clamp measurements, we discovered that PI(4,5)P2 is a positive co-factor required for the activity of TRPM3. Analogous to what is known for other ion channels; we found that TRPM3 function can also be regulated by multiple pathways. In addition to PI(4,5)P2, we discovered that the heteromeric G protein subunits, Gβγ inhibits TRPM3 ion channels. Taken together this thesis has highlighted multiple pathways that regulate TRPM3. These pathways can be further explored to understand their contribution to TRPM3 function under normal as well as pathological conditions.


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