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1 Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA
2 Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA; Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA
* To whom correspondence should be addressed. E-mail: jiaswu{at}iupui.edu.
Objective: Previous studies have demonstrated a discrete population of M cells in the ventricular midmyocardium having excessive action potential duration (APD) prolongation during long activation cycle lengths (CL) and under the influence of APD prolonging agents. However, M cells have not been found in other studies. Existing explanations do not satisfactorily explain these discrepancies. We hypothesized that instead of being a discrete group, M cells represent an extreme functional state of ventricular heterogeneity. Methods: We mapped APDs on the cut-exposed transmural surfaces of arterially perfused ventricular wedges from 26 dogs during Na+ current modification with anemone toxin II (ATX-II). Results: Compared to the endocardium, APDs were not statistically different in the parallel layer having the longest mean-APD (APDL), and were significantly shorter in the epicardium in the 26 wedges before ATX-II. ATX-II (
5 nmol/l) prolonged APD heterogeneously (mid-myocardium > endocardium > epicardium). The differences increased at longer CLs. ATX-II (20.0 nmol/l) shifted the APDL layer to 32%±6.2% (6 wedges, CL: 4000 msec) of the transmural thickness from the (sub)endocardium (8.6%±7.2%, 26 wedges, ATX-II-free). We confirmed the existence of M cells (significantly longer APDs in the APDL layer than in the endocardium and epicardium, p
0.04, CL: 4000 msec) in the 18 wedges having 5 nmol/l ATX-II, but not (p>0.36) in the other 18 wedges having 2.5 nmol/l ATX-II. Therefore, both the position of the APDL layer and presence of M cells were modulated by ATX-II. Conclusions: M cells are a dynamic functional state of ventricular heterogeneity, instead of a static anatomically discrete population.
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