The M cell: Its contribution to the ECG and to normal and abnormal electrical function of the heart

Characteristics of the M Cell. The discovery and characterization of the M cell, a unique cell type residing in the deep layers of the ventricular myo cardium, has opened a new door in our understanding of the electrophysiolog y and pharmacology of the heart in both health and disease. The hallmark of the M cell is the ability of its action potential to prolong much more tha n that of other ventricular myocardial cells in response to a slowing of ra te and/or in response to agents that act to prolong action potential durati on. Our goal in this review is to provide a comprehensive characterization of the M cell, its contribution to transmural heterogeneity, and its role i n the normal electrical function of the heart, in the inscription of the EC G (particularly the T wave), and in the development of QT dispersion, T wav e alternans, long QT intervals, and cardiac arrhythmias, such as torsades d e pointes. Our secondary goal is to address the controversy that has arisen relative to the functional importance of the M cell in the normal heart. T he controversy derives largely from the failure of some investigators to de monstrate transmural heterogeneity of repolarization in the dog in vivo und er control conditions and after administration of quinidine. The inability to demonstrate transmural heterogeneity under these conditions may be due t o the use of bipolar recording techniques that, in our experience, seriousl y underestimate transmural dispersion of repolarization (TDR). The use of s odium pentobarbital and alpha-chloralose as anesthesia also is problematic, because these agents reduce or eliminate TDR by affecting a variety of ion channel currents. Finally, attempts to amplify transmural dispersion of re polarization with an agent such as quinidine must take into account that re latively high concentrations can result in effects opposite to those desire d due to drug inhibition of multiple ion channels. These observations may e xplain the inability of earlier studies to detect the M cell.