Biology Reference
In-Depth Information
Chapter 10
Network Dynamics in Cardiac
Electrophysiology
Zhilin Qu
Abstract In a network perspective, the heart is a network of cells that are com-
posed of subnetworks of genes, proteins, metabolites, and organelles. In this
chapter, we provide an overview of the networks in the heart and a current
understanding of the network dynamics in the context of cardiac electrophysiology.
We first review current knowledge of the genetic, signaling, and metabolic
networks in the heart and their links to arrhythmias. We then review the emergent
properties from the mitochondrial and calcium release unit networks, the cellular
dynamics arising from integrated subnetworks, and the electrical dynamics arising
from the cellular networks to manifest as normal rhythms and arrhythmias. Finally,
we discuss future challenges and how systems biology approaches can overcome
these challenges to uncover the mechanisms of normal heart rhythms and
arrhythmias.
10.1
Introduction
Arrhythmias are irregular excitations in the heart, the major causes of sudden
cardiac death (Zipes and Wellens
1998
). Anti-arrhythmic drugs that block ion
channels have been shown to be ineffective, and some even increase mortality
(CAST
1989
; Waldo et al.
1996
). Defibrillators, merely based on the fact that the
heart is electrically excitable, are the only effective therapeutics. This raises a
serious question: what have been missed in our understanding of cardiac electro-
physiology? Cardiac excitations are regulated by many factors from different scales
of the heart, ranging from molecular interactions to tissue scale electrical wave
dynamics (Fig.
10.1
). At the molecular scale, proteins that form the ion channels
behave randomly due to thermodynamic fluctuations and dynamics, resulting in
Z. Qu (
*
)
Department of Medicine (Cardiology), David Geffen School of Medicine, University of
California, A2-237 CHS, 650 Charles E. Young Drive South, Los Angeles, CA 90095, USA
e-mail:
zqu@mednet.ucla.edu
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