DOI
https://doi.org/10.25772/TRFK-FZ95
Author ORCID Identifier
0000-0003-0372-607X
Defense Date
2018
Document Type
Thesis
Degree Name
Master of Science
Department
Physiology and Biophysics
First Advisor
Carlos Escalante
Second Advisor
Diomedes Logothetis
Third Advisor
Lei Zhou
Fourth Advisor
Srinivasa Karnam
Fifth Advisor
Hamid Akbarali
Sixth Advisor
Fadi Salloum
Abstract
Hydrogen sulfide (H2S) reduces ischemia reperfusion (IR) injury by stimulating adenosine triphosphate (ATP) sensitive potassium channels (KATP) [1-5]. Demonstrating H2S stimulation is unique to KATP, as other inwardly rectifying potassium (Kir) channels demonstrate inhibition or are unaffected [6]. We recently showed that H2S inhibits Kir2 and Kir3 by decreasing channel sensitivity to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 or PIP2) [6]. Here, we test the hypothesis that H2S regulation of Kir6.2, a pore-forming subunit of the KATP channel, is also dependent on PIP2. Using whole-cell patch-clamp we show that H2S increases the activity of Kir6.2 channels expressed in HEK-293 cells. To study the mechanism, we modulated PIP2 levels by expressing a light- activated phosphatase, or by including high levels of a water-soluble PIP2 analog in the patch pipette. The results suggest that H2S augmentation of Kir6.2 channel activity is increased when PIP2 levels are elevated.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
7-28-2018