Electrophysiology of Myocardial Cells in the Epicardial, Midmyocardial, and Endocardial Layers of the Ventricle

The recent discovery of multiple myocardial cell types in the ventricular wall of most species has prompted a reevaluation of several electrophysiologic and electrocardiographic findings. This review briefly presents the salient electrophysiologic features of myocardial cells in the epicardial, midmyocardial and endocardial regions of the ventricle. The epicardial action potential exhibits a prominent notch between phase I and phase 2 that results in a spike and dome configuration. The notch is smaller in midmyocardial cells and absent in endocardial cells. The action potential notch is due to the presence of a transient outward current (I_to), which diminishes in amplitude from the epicardial to endocardial surfaces. Midmyocardial or "M cells" exhibit electrophysiologic features intermediate between those of myocardial and conducting cells. M cells differ from epicardial and endocardial cells primarily in their response to slowing of the stimulation rate. These cells display an exaggerated prolongation of action potential duration at moderate to slow rates of stimulation. The atypical response in M cells reflects decreased levels of the delayed rectifier K⁺ current (I_K) in this cell type. Another distinguishing feature of M cells is a greater rate of rise of the upstroke of phase 0 (dV/dt) compared to epicardial or endocardial cells. These electrophysiologic distinctions contribute to differences in the responsiveness of the various cell types to pharmacologic agents and disease. Also, the dispersion of repolarization created between epicardium and endocardium in the early phases of the action potential, and between M cells and other ven tricular layers during late repolarization, may explain the J wave and U wave of the electro cardiogram, respectively.