Graduate Studies Bulletin Announcement
The role of endothelin signaling in murine Purkinje fiber development.
Abstract
Rita Patel
Approximately 220,000 people
a year die of coronary heart disease (CHD) in the US alone. One class of CHD is
characterized by sudden cardiac death (cardiac arrest) due to either
ventricular tachycardia or ventricular fibrillation. Cardiac arrhythmias are a
different class of cardiac abnormalities that can also lead to CHD. Over 2
million people in the US today suffer from cardiac arrhythmias, presenting an
irregular heartbeat. To date, potential treatments include electronic devices
such as cardioverter defibrillators that are implanted under the skin in order
to restore normal cardiac rhythms. A malformation in cardiac Purkinje fibers
has been implicated as the cause of such arrhythmias. Purkinje fibers are specialized impulse conducting cells located
in the interventricular septum and the ventricular myocardium of the heart.
They are important in the maintenance of a regular heartbeat by coordinating
ventricular contractions. The development of Purkinje fibers is a highly
regulated process. There is good evidence that during chick embryogenesis
Purkinje fibers are recruited from cardiomyocytes located spatially in
association with developing coronary arteries. In the chick, it has also been
shown that the cytokine Endothelin-1 (ET-1) is responsible for Purkinje fiber
recruitment from cardiomyocytes.
In this study, I propose to
investigate whether, like in the avian system, ET-1 can convert murine
cardiomyocytes into Purkinje fibers. I will establish ET-1 induced and
non-induced primary embryonic cardiomyocyte cultures and compare the expression
of cardiomyocyte and Purkinje fiber specific genes. The expression of the
Purkinje fiber specific genes connexins
40 and 45, HF-1b, and minK as well
as the cardiomyocyte specific gene cardiac
myosin binding protein C will be detected by immunohistochemistry and in
situ hybridization, and analyzed by confocal microscopy. The upregulation
of Purkinje fiber specific genes and downregulation of cardiomyocyte specific
genes in treated cultures will indicate that ET-1 may be involved in the
differentiation process of Purkinje fibers. The results obtained in this study
will allow us to better understand the molecular mechanisms underlying the
development of the mammalian heart conduction system and could eventually lead
to alternative forms of treatments for cardiac arrhythmias.
Date:
May 8, 2002 Department:
Biological Sciences
Place:
WC 130 Major
Professor: Dr. Lidia Kos
Time:
10.00 a.m.