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Cardiovascular Research 2000 45(4):952-960; doi:10.1016/S0008-6363(99)00418-6
© 2000 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

M cells and transmural heterogeneity of action potential configuration in myocytes from the left ventricular wall of the pig heart

Tania Stankovicova1, Monika Szilard, I De Scheerder and Karin R Sipido*

Laboratory of Experimental Cardiology, University of Leuven, Campus Gasthuisberg O/N 7th floor, Herestraat 49, B-3000 Leuven, Belgium

* Corresponding author. Tel.: +32-16-347-153; fax: +32-16-345-844 karin.sipido{at}med.kuleuven.ac.be

Objective: Heterogeneity of action potential configuration in the left ventricle (LV), and the contribution of M cells to it, has been observed in the human heart and is important for arrhythmogenesis. Whether the pig heart has similar properties remains a controversial but important issue as the pig heart is currently under study for use in xenotransplantation. Methods: Single myocytes were enzymatically isolated from the epicardium (EPI, ncells=29), midmyocardium (MID, ncells=38), and endocardium (ENDO, ncells=13) of the free LV wall (npigs=26, 14–22 weeks old, 55–80 kg), and studied at different stimulation rates during whole-cell recording (normal Tyrode's solution, K+-aspartate-based pipette solution, 50 µM K5fluo-3 as [Ca2+]i indicator, 37°C). Standard six-lead ECGs were recorded from anesthetized pigs. Results: The action potential duration (APD) was not significantly different at 0.25 Hz vs. 2 Hz for the majority of cells in all three layers. However, a subpopulation of cells behaved like M cells and had a very steep frequency response (APD90 at 0.25 Hz 538±30 ms, vs. 337±9 ms at 2 Hz, P<0.05, n=22). These cells were found predominantly in the MID layer (34% of cells), but also (24%) in EPI. M cells had a more pronounced spike-and-dome configuration, with a significantly larger phase 1 magnitude and plateau voltage. The frequency response of these parameters was different from the other cell types. [Ca2+]i transients tended to be larger in M cells. For the in vivo ECG of anesthetized pigs, the QT time was close to the APD90 of M cells, and J waves were seen in 7/12 recordings. Conclusions: In young adult pigs, M cells can be identified by a steep frequency response of the APD and by a spike-and-dome configuration. These cells are mostly, but not exclusively, found in the midmyocardium, and could contribute to the ECG characteristics. Their properties may however be different from those of other species, including humans.

KEYWORDS Membrane potential; Myocytes; ECG


1 Present address: Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic.


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