Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle.
Action potentials and whole cell sodium current were recorded in canine epicardial, midmyocardial, and endocardial myocytes in normal sodium at 37 degrees 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 microM 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.
Zygmunt
A C
AC
Department of Experimental Cardiology, Masonic Medical Research Laboratory, Utica, New York 13501-1787, USA. zygmunt@mmrl.edu
Eddlestone
G T
GT
Thomas
G P
GP
Nesterenko
V V
VV
Antzelevitch
C
C
D000200:Action Potentials; D000818:Animals; D004285:Dogs; D006329:Heart Conduction System / Q000502:physiology*; D008133:Long QT Syndrome / Q000503:physiopathology; D008297:Male; D012964:Sodium / Q000502:physiology; D016276:Ventricular Function
D012964:Sodium