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Increasing I(Ks) corrects abnormal repolarization in rabbit models of acquired LQT2 and ventricular hypertrophy.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2002 Aug; Vol. 283 (2), pp. H664-70. - Publication Year :
- 2002
-
Abstract
- 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.
- Subjects :
- Action Potentials drug effects
Animals
Benzodiazepines pharmacology
Delayed Rectifier Potassium Channels
Electrophysiology
Long QT Syndrome classification
Male
Potassium Channels drug effects
Rabbits
Reaction Time drug effects
Hypertrophy, Left Ventricular physiopathology
Long QT Syndrome physiopathology
Potassium Channels metabolism
Potassium Channels, Voltage-Gated
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 283
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12124214
- Full Text :
- https://doi.org/10.1152/ajpheart.00076.2002