Beat-to-beat repolarization variability in ventricular myocytes and its suppression by electrical coupling.
Single ventricular myocytes paced at a constant rate and held at a constant temperature exhibit beat-to-beat variations in action potential duration (APD). In this study we sought to quantify this variability, assess its mechanism, and determine its responsiveness to electrotonic interactions with another myocyte. Interbeat APD(90) (90% repolarization) of single cells was normally distributed. We thus quantified APD(90) variability as the coefficient of variability, CV = (SD/mean APD(90)) x 100. The mean +/- SD of the CV in normal solution was 2.3 +/- 0.9 (132 cells). Extracellular TTX (13 microM) and intracellular EGTA (14 mM) both significantly reduced the CV by 44 and 26%, respectively. When applied in combination the CV fell by 54%. In contrast, inhibition of the rapid delayed rectifier current with L-691,121 (100 nM) increased the CV by 300%. The CV was also significantly reduced by 35% when two normal myocytes were electrically connected with a junctional resistance (R(j)) of 100 MOmega. Electrical coupling (R(j) = 100 MOmega) of a normal myocyte to one producing early afterdepolarization (EAD) completely blocked EAD formation. These results indicate that beat-to-beat APD variability is likely mediated by stochastic behavior of ion channels and that electrotonic interactions act to limit temporal dispersion of refractoriness, a major contributor to arrhythmogenesis.
Zaniboni
M
M
Department of Evolutive and Functional Biology, University of Parma, Parma, Italy 43100.
Pollard
A E
AE
Yang
L
L
Spitzer
K W
KW
D000200:Action Potentials; D000818:Animals; D002450:Cell Communication; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity; D017097:Electric Impedance; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D007473:Ion Channels / Q000502:physiology; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D010881:Piperidones / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D016276:Ventricular Function
D007473:Ion Channels; D010881:Piperidones; D013141:Spiro Compounds; C077569:L 691121; D013779:Tetrodotoxin; D004533:Egtazic Acid