Date of Award

7-2022

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Shu Zhu MD, PhD

Second Advisor

Richard E. White, PhD, FAHA

Third Advisor

Xinyu (Eric) Wang, PhD

Fourth Advisor

Lori Redmond, PhD

Abstract

Human pulmonary artery smooth muscle cells (HPASMC) maintain the vascular tone and exhibit myogenic reactivity in the pulmonary arteries. The BKCa channel, being the predominate K+ channel within the HPASMC, is important in regulating the pulmonary arterial pressure and because the BKCa channel’s activity can be modulated by various molecules, studies have evaluated the role that altered BKCa channel expression and function plays in the dysfunction of the HPASMC during type 2 diabetes (T2D). The results from those studies provided a basis for this project. In this study, cell cultures, western blot experiments, and cAMP assays were employed to evaluate the BKCa channel expression and function in HPASMC from a non-diabetic individual (NHPASMC) and HPASMC from a type 2 diabetic individual (D2HPASMC). In the western blot results, there was altered expression of the BKCa channel α- and β1-subunits in the D2HPASMC. In the cAMP assay results, following exposure to a known adenylate cyclase activator, cAMP levels were increased in the NHPASMC and D2HPASMC, but the D2HPASMC exhibited overall lower cAMP levels. These alterations to the BKCa channel’s expression and function provide further support that impaired BKCa channel function may contribute to dysfunction of the vascular smooth muscle in the pulmonary arteries that may then lead to the development of pulmonary hypertension.

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