Page 5 - YORAM RUDY BOOK FINAL

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1. PROLOGUE

“The heart of all creatures is the foundation of their life;

from whence all strength and vigor flows”

— William Harvey
In “An anatomical disputation concerning the movement
of the heart and the blood in living creatures“, 1653

Mechanical contraction of the heart and its blood-pumping action are activated and
synchronized by a wave of electrical excitation. Propagation of the excitation wave involves
action potential (AP) generation by cardiac cells and its conduction in the multicellular tissue.
AP generation is accomplished through complex, non-linear interactions between membrane

ion channels, transmembrane voltage, and the dynamically-changing ionic milieu of the cell. AP
propagation is achieved by flow of electrical charge from cell-to-cell through intercellular gap
junctions. As described in this monograph, the propagation process involves strong interactions

within and across scales between the molecular structure and function of ion channels, the
properties of gap junctions, the sub-cellular organization of the cell, and the tissue architecture.
At the whole-heart scale, normal excitation is generated in the right atrium by the sino-atrial (SA)
node and transmitted to the ventricles through the atrio-ventricular (AV) node. It then spreads
rapidly via the specialized conduction (Purkinje) system to establish broad excitation wavefronts

that propagate synchroneously from endocardium to epicardium in both ventricles. Abnormal
1,2
electrical activity can originate at any scale of this system, possibly leading to cardiac rhythm
irregularities that could be fatal (cardiac arrhythmias are one of the most frequent causes of

morbidity and mortality in the human population).

During the cardiac excitation process, current sources arise in cell membranes throughout
the heart. These sources generate an electric field in the conducting medium surrounding the
heart and in particular on the body surface, where it can be recorded as the electrocardiogram

(ECG). Similarly, isolated cell or tissue preparations generate potential waveforms in the
surrounding medium during excitation (e.g. in the bath solution). Thus, the cardiac action potential
and the activity of ion channels that underlies its generation are reflected in these extracellular

potential fields.

This monograph attempts to establish and describe the biophysical principles and
mechanisms that underlie action potential generation and propagation in cardiac tissue and the
associated electric fields. Computational biology is used to establish relationships across scales

from the molecular structure of ion-channel proteins, to the cell, to the multicellular tissue.