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- W2058193259 abstract "Introduction: LQT1 and LQT2 syndromes, the two most common inherited long QT syndromes, are associated with sudden cardiac death (SCD) due to torsade de pointes (TdP). We investigated the role of EADs and triggered activity in the pathogenesis of arrhythmia in myocytes derived from transgenic rabbit models of LQT1 and LQT2. Method: We used classic whole cell patch-clamp techniques to study EAD and triggered activity in single myocytes in Tyrode's solution with 3.6 mM K+. Cardiomyocytes were derived from LQT1, LQT2 and littermate control (LMC) rabbits. Results: Under extracellular K+ concentration of 3.6 mM, EADs were observed in 13 out of 16 LQT2 myocytes, and spontaneous TdP-like membrane potential oscillations with a frequency of ∼2-3 Hz were observed in one myocyte following the appearance of an EAD (see figure). By contrast, no EADs were observed in 11 LQT1 myocytes and 17 LMC myocytes under these conditions. Incubation with 50 nM of isoproterenol (ISO), however, induced EADs in 3 out of 11 LQT1 myocytes but in none of the 17 LMC myocytes. Spontaneous TdP-like membrane potential oscillation with similar frequency was also observed in one LQT1 myocyte with ISO incubation following the appearance of an EAD. The average action potential duration at 90% repolarization was 536.05±32.54 ms (n=17) in LMC cells, 1013.18±98.88 ms (n=11, p<0.05 vs. LMC) in LQT1 cells, and 1292.09 ± 189.52 ms at 34±1°C (n=16, p<0.05 vs. LMC). Conclusion: EADs and triggered activity tend to occur in LQT2 myocytes under basic conditions, while triggered activity in LQT1 myocytes requires sympathetic stimulation. Both LQT1 and LQT2 myocytes demonstrate the potential for continuous membrane oscillation once EADs are induced." @default.
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- W2058193259 date "2010-01-01" @default.
- W2058193259 modified "2023-09-26" @default.
- W2058193259 title "Differential Conditions for EAD and Triggered Activity in Cardiomyocytes Derived from Transgenic LQT1 and LQT2 Rabbits" @default.
- W2058193259 doi "https://doi.org/10.1016/j.bpj.2009.12.2861" @default.
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