The ionic mechanisms of early after depolarization in mouse ventricular myocytes: the role of IK1.
The occurrence of early after depolarization (EAD) in single mouse ventricular myocytes was observed and its ionic mechanisms were studied using the patch clamp technique. Under treatment with perfusion of Tyrode's solution containing 3 mM KCl and 3 mM CsCl, 3/6 cases exhibited EAD, while with 3 mM KCl or 3 mM CsCl alone, EAD was not induced. The background steady-state current-voltage (I-V) curves of the myocytes showed no negative slope, i.e., the slope in the range of 50 mV positive to the reversal potential was virtually flat and stayed at a low current level. Under perfusion of 3 mM KCl and 3 mM CsCl, the outward current in the above region decreased nearly to 0: in the myocytes which exhibited EAD, a net inward current (crossover) was displayed in the same region, which was abolished by 10 microM TTX and 10 microM nifedipine. The results of whole-cell inward rectifier current I-V curves were similar to the above background steady-state I-V curves. In mouse ventricular myocytes, transient outward current was very strong with a peak current density of 63 +/- 19 pA/pF, whereas low K+ and Cs+ had no significant effect. 11/30 cases showed obvious delayed rectifier current, but the tail current recorded by envelope method was relatively weak (1.19 +/- 0.35 pA/pF) and insensitive to CsCl or changing of the KCl concentration. The results suggest that under treatment with low K+ and Cs+, the inhibition of inward rectifier current is the basis of the formation of second plateau, while Na and Ca currents contribute to the generation of triggered bursts.
Zhou
Y Y
YY
Laboratory of Biomembrane and Membrane Engineering, College of Life Sciences, Peking University, P.R. China.
Liu
T F
TF
D000818:Animals; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology
D002712:Chlorides; D007473:Ion Channels; D002586:Cesium; D011189:Potassium Chloride; C028019:cesium chloride