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(Circulation Research. 2000;87:964.)
© 2000 American Heart Association, Inc.

Editorial

Electrical Heterogeneity, Cardiac Arrhythmias, and the Sodium Channel

Charles Antzelevitch

From the Masonic Medical Research Laboratory, Utica, NY.

Correspondence to Dr Charles Antzelevitch, Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501.

Key Words: heterogeneity • sodium channels • cardiac arrhythmias

	Introduction

 
It was not long ago that we thought of the ventricles of the heart as being composed of 2 basic cell types: specialized conducting cells that make up the His-Purkinje system and ventricular myocytes. Studies conducted over the last decade have highlighted the diversity among the cells that comprise the ventricular myocardium, pointing to regional differences in the electrical properties of cells as well as major distinctions in the response to pharmacological agents and pathophysiological states.^{1 2} Several interesting differences have been described between endocardium and epicardium, and a unique population of cells located in the midmyocardial layers has been identified and shown to display electrophysiological and pharmacological profiles different from those of epicardium and endocardium. These cells, known as M cells, have been observed in canine, guinea pig, rabbit, pig, and human ventricles.^{3 4 5 6 7 8}

Epicardial, endocardial, and M cells differ in several ways, but principally with respect to repolarization characteristics. Ventricular epicardial and M cells display action potentials with a prominent transient outward current (I_to)-mediated phase 1, giving rise to a notched appearance of the action potential. The absence of a prominent notch in endocardium is a consequence of a much smaller I_to. Similar regional differences in I_to are found in canine, feline, rabbit, rat, and human ventricular myocytes.¹ Recent studies also indicate that I_to and the action potential notch are much larger in right versus left ventricular epicardial⁹ and M¹⁰ cells. The transmural gradient in the amplitude of the I_to-mediated action potential notch underlies the normal . . . [Full Text of this Article]

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