Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle

Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, New York 13501-1787 Action potentials and whole cell sodium current were recorded in canine epicardial, midmyocardial, and endocardial myocytes in normal sodium at 37°C. Tetrodotoxin (TTX) reduced the action potential...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2001-08, Vol.281 (2), p.H689-H697
Main Authors: Zygmunt, Andrew C, Eddlestone, Geoffrey T, Thomas, George P, Nesterenko, Vladislav V, Antzelevitch, Charles
Format: Article
Language:English
Subjects:
Action Potentials
Animals
Dogs
Heart Conduction System - physiology
Long QT Syndrome - physiopathology
Male
Sodium - physiology
Ventricular Function
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Summary:Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, New York 13501-1787 Action potentials and whole cell sodium current were recorded in canine epicardial, midmyocardial, and endocardial myocytes in normal sodium at 37°C. Tetrodotoxin (TTX) reduced the action potential duration of midmyocardial cells to a greater degree than either epicardial or endocardial cells. Whole cell recordings in potassium-free and very-low-chloride solutions revealed a slowly decaying current that was completely inhibited by 5 µM TTX or replacement of external and internal sodium with the impermeant cation N -methyl- D -glucamine. Late sodium current density at 0   mV was 47% greater in midmyocardial cells and averaged 0.532   ± 0.058 pA/pF in endocardial, 0.463 ± 0.068 pA/pF in epicardial, and 0.785 ± 0.070 pA/pF in midmyocardial cells. Neither the frequency dependence of late sodium current nor its recovery from inactivation exhibited transmural differences. After a 4.5-s pulse to 30 mV, late sodium current recovered with a single time constant of 140   ms. We conclude that a larger late sodium conductance in midmyocardial cells will favor longer action potentials in these cells. More importantly, drugs that slow inactivation of sodium channels will produce a nonuniform response across the ventricular wall that is proarrhythmic. myocytes; transmural heterogeneity; tetrodotoxin-sensitive current; long Q-T syndrome
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.2001.281.2.h689