Increasing I Ks corrects abnormal repolarization in rabbit models of acquired LQT2 and ventricular hypertrophy

Excessive action potential (AP) prolongation and early afterdepolarizations (EAD) are triggers of malignant ventricular arrhythmias. A slowly activating delayed rectifier K + current ( I Ks ) is important for repolarization of ventricular AP. We examined the effects of I Ks activation by a new benzo...

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Published in:American journal of physiology. Heart and circulatory physiology 2002-08, Vol.283 (2), p.H664-H670
Main Authors: Xu, Xiaoping, Salata, Joseph J., Wang, Jixin, Wu, Ying, Yan, Gan-Xin, Liu, Tengxian, Marinchak, Roger A., Kowey, Peter R.
Format: Article
Language:English
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Summary:Excessive action potential (AP) prolongation and early afterdepolarizations (EAD) are triggers of malignant ventricular arrhythmias. A slowly activating delayed rectifier K + current ( I Ks ) is important for repolarization of ventricular AP. We examined the effects of I Ks activation by a new benzodiazepine (L3) on the AP of control, dofetilide-treated, and hypertrophied rabbit ventricular myocytes. In both control and hypertrophied myocytes, L3 activated I Ks via a negative shift in the voltage dependence of activation and a slowing of deactivation. L3 had no effect on L-type Ca 2+ current or other cardiac K + currents tested. L3 shortened AP of control, dofetilide-treated, and hypertrophied myocytes more at 0.5 than 2 Hz. Selective activation of I Ks by L3 attenuates prolonged AP and eliminated EAD induced by rapidly activating delayed rectifier K + current inhibition in control myocytes at 0.5 Hz and spontaneous EAD in hypertrophied myocytes at 0.2 Hz. Pharmacological activation of I Ks is a promising new strategy to suppress arrhythmias resulting from excessive AP prolongation in patients with certain forms of long QT syndrome or cardiac hypertrophy and failure.
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00076.2002