University of Illinois Urbana-Champaign

Defining a role for the cystic fibrosis transmembrane conductance regulator in the heart

Sellers, Zachary M.

Content Files
1_Sellers_Zachary.pdf

Permalink

https://hdl.handle.net/2142/15519

Description

Title
Defining a role for the cystic fibrosis transmembrane conductance regulator in the heart
Author(s)
Sellers, Zachary M.
Issue Date
2010-05-14T20:43:58Z
Director of Research (if dissertation) or Advisor (if thesis)
Best, Philip M.
Doctoral Committee Chair(s)
Best, Philip M.
Committee Member(s)
  • Xiang, Yang
  • Cox, Charles L.
  • Nelson, Deborah
Department of Study
Molecular & Integrative Physl
Discipline
Molecular & Integrative Physi
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2010-05-14T20:43:58Z
Keyword(s)
  • cystic fibrosis
  • Cystic fibrosis transmembrane conductance regulator (CFTR)
  • cardiac myocyte
  • heart
Abstract
While cystic fibrosis (CF) is commonly thought of as a lung disease, since it’s first description 70 years ago we have come to understand that loss of CFTR (cystic fibrosis transmembrane conductance regulator) function affects numerous tissues and systems throughout the body. Concerning the heart, right ventricular dysfunction secondary to pulmonary abnormalities has long been recognized. However, the issue as to whether loss of CFTR function causes primary disturbances in the heart has remained an unsolved and often debated question. Thus, the goal of the research presented herein was to answer two fundamental questions, 1) “Does CFTR play a physiological role in heart function?,” and 2) “What direct impact does loss of CFTR activity have on heart function?” These are particularly timely questions now as CF patients are living longer and the development of CFTR modulators is being pursued with increased vigor. Thus, an understanding if CF patients will be at increased risk for heart disease and whether new therapies may affect heart function are of direct relevance to the care of these individuals. To begin to answer the questions presented we have examined how modulation of CFTR affects neonatal ventricular cardiomyocyte contraction rate. We found that CFTR is involved in the regulation of both baseline and beta-adrenergic stimulated contraction rate. Additionally, loss of CFTR activity, whether acutely or chronically, leads to modulation of intracellular signaling molecules and other Cl- channels, which in some cases can completely compensate for this loss, while in other cases cannot. Finally, in vivo examination of heart function in CFTR KO mice has elucidated disturbances in heart structure and function, which may translate into problems experienced by CF patients. In sum, this work presents a significant expansion of our understanding regarding the role of CFTR in heart function and highlights the need to further pursue a more in-depth analysis of the health of the heart in CF patients.
Graduation Semester
2010-05
Permalink
http://hdl.handle.net/2142/15519
Copyright and License Information
Copyright 2010 Zachary M. Sellers

Owning Collections

Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Molecular and Integrative Physiology