Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


kent1228141040.pdf (88.49 MB)

ETD Abstract Container

Abstract Header

Expression and Phosphorylation of Left Atrial Connexin 43 in Human and Experimental Atrial Fibrillation

Ram, Rashmi
http://rave.ohiolink.edu/etdc/view?acc_num=kent1228141040

Abstract Details

2008, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Background: Atrial fibrillation (AF) is a prevalent and increasingly common arrhythmia that increases risk of stroke and death. Electrical and structural remodeling processes contribute to the development of persistent AF. Remodeling promotes heterogeneous ion channel activity and conduction that form a substrate for re-entrant activity. Connexins are proteins that underlie conduction between myocytes; conduction is regulated by connexin expression and phosphorylation. Connexin 43 (Cx43) is the most abundant cardiac connexin. We tested the hypothesis that left atrial (LA) expression and/or phosphorylation of Cx43 is dynamically modulated in human AF, and in two animal models of AF. Methods: Histologic, confocal and western analyses were performed to examine the expression, phosphorylation and distribution of Cx43 in LA tissues from cardiac surgery patients (i) with or without a history of AF, (ii) in sinus rhythm or AF at surgery. Left and right atrial Cx43 expression, distribution and phosphorylation was also evaluated in a goat model of short- and long-term AF, and in a canine model of post-surgical AF. Results: Our studies demonstrate that: (i) atrial rhythm acutely modulates Cx43 expression and phosphorylation, (ii) Cx43 expression tends to increase within three weeks of AF, and redistributes to the lateral surface of myocytes with prolonged AF, (iii) Cx43 is present not only in the intercalated disk, but also in the mitochondria of both human and canine atria, (iv) C-reactive protein is detectable in the LA of patients with human AF, and its presence reflects current rhythm, (v) inflammation in the setting of post-operative AF modulates Cx43 expression and phosphorylation differently in left and right atria, and (vi) dietary supplementation with ω3-PUFAs attenuates basal Cx43 expression and phosphorylation, likely enhancing the safety factor of conduction, thus limiting arrhythmia inducibility. Conclusions: Cx43 expression and phosphorylation are dynamically modulated by stresses imposed by abnormal hemodynamics, autonomic tone, heart rate and inflammation. Redistribution of Cx43 likely affects the anisotropic properties of atrial conduction, and contributes to the development of persistent atrial fibrillation. Expression of Cx43 in cardiac mitochondria suggests that it may have additional important functions within the myocyte, beyond its widely appreciated role as mediator of cell-to-cell coupling.
David R. Van Wagoner, PhD (Advisor)
265 p.
Biomedical Research
Connexin 43; Inflammation; Atrial Fibrillation

Recommended Citations

Citations

  • Ram, R. (2008). Expression and Phosphorylation of Left Atrial Connexin 43 in Human and Experimental Atrial Fibrillation [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1228141040

    APA Style (7th edition)

  • Ram, Rashmi. Expression and Phosphorylation of Left Atrial Connexin 43 in Human and Experimental Atrial Fibrillation. 2008. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1228141040.

    MLA Style (8th edition)

  • Ram, Rashmi. "Expression and Phosphorylation of Left Atrial Connexin 43 in Human and Experimental Atrial Fibrillation." Doctoral dissertation, Kent State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=kent1228141040

    Chicago Manual of Style (17th edition)

kent1228141040
542
© 2008, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.