Distribution of M Cells in the Canine Ventricle

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Abstract
M cells and transitional cells residing in the deep structures of the ventricular free walls are distinguished by the ability of their action potentials to prolong disproportionately to those of other ventricular cells at relatively slow rates. This feature of the M cell due, at least in part, to a smaller contribution of the slowly activating component of the delayed rectifier current (IKs) is thought to contribute to the unique pharmacologic responsiveness of M cells, making them the primary targets in ventricular myocardium for agents that cause action potential prolongation and induce early and delayed afterdepolarizations and triggered activity. Previous studies dealt exclusively with the characteristics and distribution of M cells in the canine right and left ventricular free wall near the base of the ventricles. The present study uses standard microelectrode techniques to define their behavior and distribution in the apical region of the ventricular wall as well as in the endocardial structures of the ventricle, including the interventricular septum, papillary muscles, and trabeculae. Action potentials recorded from the M region (deep subepicardium) displayed similar characteristics (steep action potential duration [APD]-rate relations) in the base and apex. However, important differences were apparent in the other regions. In epicardium, the spike and dome morphology of the action potential was less accentuated and the rate dependence of APD more pronounced in the apex versus the base. In endocardium, and especially deep subendocardium, rate dependence of APD was considerably more pronounced in the apex. Transmembrane recordings from the subsurface layers of the septum, trabeculae, and papillary muscles revealed M cell behavior (steep APD-rate relations) in the deep subendocardium. Epicardial and transitional behavior were also observed in the deep layers of these endocardial structures. Our results indicate that M cells reside throughout the deep subepicardial layers of the free wall of the canine left ventricle as well as in the deep subendocardial layers of the septum, papillary muscles, and trabeculae. The data also demonstrate prominent transmural as well as apicobasal gradients of phase 1 and phase 3 repolarization. These findings may have implications relative to our understanding of the electrocardiographic J wave, T wave, U wave, and long QTU intervals.