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

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