Functional and transmural modulation of M cell behavior in canine ventricular wall.
Previous studies have demonstrated a discrete population of midmyocardial (M) cells in the ventricular myocardium 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 for the discrepancies appear inadequate. We hypothesized that instead of being a discrete group, M cell behavior is functional and conditionally expressed. 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). Compared with 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 (> or =5 nmol/l) prolonged APD heterogeneously (midmyocardium > endocardium > epicardium). The differences increased at longer CLs. ATX-II (20.0 nmol/l) shifted the APD(L) layer to 32 +/- 6.2% (6 wedges, CL: 4,000 ms) of the transmural thickness from the (sub)endocardium (8.6 +/- 7.2%, 26 wedges, ATX-II free). We detected the presence of M cell behavior (significantly longer APDs in the APDL layer than in the endocardium and epicardium, P < or = 0.04, CL: 4,000 ms) in the 18 wedges having > or =5 nmol/l ATX-II but not (P >0.36) in the other 18 wedges having < or =2.5 nmol/l ATX-II. Both the position of the APDL layer and presence of M cell-like behavior were modulated by ATX-II. The dynamic spatial modulation indicates that M cell behavior is functional and only becomes manifest under suitable conditions.
Krannert Institute of Cardiology, Indiana Univ. School of Medicine, 1800 N. Capitol Ave., Indianapolis, IN 46202, USA.
Norihiro
N
Ueda
Douglas P
DP
Zipes
Jiashin
J
Wu
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D003064:Cnidarian Venoms / Q000494:pharmacology; D004285:Dogs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D008133:Long QT Syndrome / Q000503:physiopathology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D016276:Ventricular Function
D002316:Cardiotonic Agents; D003064:Cnidarian Venoms; C028800:toxin II (Anemonia sulcata); D012964:Sodium