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INTRODUCTION

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Cardiac cells undergo depolarization and repolarization to form cardiac action potentials ~60 times/min. The shape and duration of each action potential are determined by the activity of ion channel protein complexes in the membranes of individual cells, and the genes encoding most of these proteins now have been identified.

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Arrhythmias can range from incidental, asymptomatic clinical findings to life-threatening abnormalities. In some human arrhythmias, precise mechanisms are known, and treatment can be targeted specifically against those mechanisms. In other cases, mechanisms can be only inferred, and the choice of drugs is based largely on the results of prior experience. Anti-arrhythmic drug therapy can have 2 goals: termination of an ongoing arrhythmia or prevention of an arrhythmia. Unfortunately, anti-arrhythmic drugs not only help to control arrhythmias but also can cause them, especially during long-term therapy. Thus, prescribing anti-arrhythmic drugs requires that precipitating factors be excluded or minimized, that a precise diagnosis of the type of arrhythmia be made, and that the risks of drug therapy can be minimized.

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PRINCIPLES OF CARDIAC ELECTROPHYSIOLOGY

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The flow of ions across cell membranes generates the currents that make up cardiac action potentials. Most anti-arrhythmic drugs affect more than one ion current, and many exert ancillary effects such as modification of cardiac contractility or autonomic nervous system function. Thus, anti-arrhythmic drugs usually exert multiple actions and can be beneficial or harmful in individual patients.

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THE CARDIAC CELL AT REST: A K+-PERMEABLE MEMBRANE

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The normal cardiac cell at rest maintains a transmembrane potential ~80-90 mV negative to the exterior; this gradient is established by pumps, especially the Na+,K+-ATPase, and fixed anionic charges within cells. There are both an electrical and a concentration gradient that would move Na+ ions into resting cells (Figure 29–1). However, Na+ channels, which allow Na+ to move along this gradient, are closed at negative transmembrane potentials, so Na+ does not enter normal resting cardiac cells. In contrast, a specific type of K+ channel protein (the inward rectifier channel) is in an open conformation at negative potentials. Hence, K+ can move through these channels across the cell membrane at negative potentials in response to either electrical or concentration gradients.

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Figure 29–1

Electrical and chemical gradients for K+ and Na+ in a resting cardiac cell. Inward rectifier K+ channels are open (left), allowing K+ ions to move across the membrane and the transmembrane potential to approach EK. In contrast, Na+ does not enter the cell despite a large net driving force because Na+ channel proteins are in the closed conformation (right) in resting cells.

Graphic Jump Location
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For each individual ion, there is an equilibrium potential Ex at which there ...

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