Electrophysiologic Characteristics of M Cells in the Canine Left Ventricular Free Wall

INTRODUCTION: Recent studies have described the existence of M cells in the deep structures of the canine and human ventricle. The present study was designed to further characterize the M cell with respect to its distribution across the canine left ventricular free wall and the dependence of its action potential on K+o. METHODS AND RESULTS: We used standard microelectrode techniques to record transmembrane activity from deep subepicardial or transmural strips isolated from the canine left ventricular free wall near the base as well as subendocardial Purkinje fibers. M cells behavior (steep APD-rate relation) was observed at depths of 1 to 7 mm from the epicardial surface (deep subepicardium to mid-myocardium). M cells were found to be distributed uniformly in the deep subepicardium and did not appear in discrete bundles. We observed transitional behavior throughout the wall. The maximum rate of rise of the action potential upstroke, Vmax, increased sharply between epicardium and deep subepicardium (176 +/- 13 to 332 +/- 61 V/sec), remained high throughout the mid-myocardium and deep subendocardium, and returned to lower values only in the superficial layers of the endocardium (205 +/- 21 V/sec). The relationship between Vmax and takeoff potential in the M cell was fit by a Boltzmann equation with a V0.5 of -68.6 +/- 1.5 mV and k of 3.4 +/- 0.5. The relationship between resting membrane potential (RMP) and K+o in the M cell was exponential from 8 to 20 mmol/L (58 mV change in RMP per 10-fold change in K+o), deviating from K+ electrode behavior at K+o < 8 mmol/L. RMP in M cells continued to hyperpolarize at K+o < 2.5 mmol/L, reaching potentials of approximately -110 mV at K+o of 1 mmol/L. In contrast, subendocardial Purkinje fibers depolarized at these low levels of K+o. Unlike endocardium and epicardium, M cells developed early afterdepolarizations at low K+o and slow rates. CONCLUSIONS: Our data indicate that the M cells are widely distributed in the intramural layers of the canine left ventricular free wall. M cells and transitional cells occupy 30% to 40% of the left ventricular wall and an estimated 20% to 40% of the mass of the ventricles of the normal canine heart. They display characteristics common to both myocardial and specialized conducting cells. Like Purkinje fibers, M cells exhibit a relatively large Vmax and steep APD-rate relations that are modulated by K+o. Unlike Purkinje fibers, M cells do not appear in bundles, they do not depolarize at K+o < 2.5 mmol/L, nor do they exhibit phase 4 depolarization.