Downregulation of delayed rectifier K(+) currents in dogs with chronic complete atrioventricular block and acquired torsades de pointes.
BACKGROUND
Acquired QT prolongation enhances the susceptibility to torsades de pointes (TdP). Clinical and experimental studies indicate ventricular action potential prolongation, increased regional dispersion of repolarization, and early afterdepolarizations as underlying factors. We examined whether K(+)-current alterations contribute to these proarrhythmic responses in an animal model of TdP: the dog with chronic complete atrioventricular block (AVB) and biventricular hypertrophy.


RESULTS
The whole-cell K(+) currents I(TO1), I(K1), I(Kr), and I(Ks) were recorded in left (LV) and right (RV) ventricular midmyocardial cells from dogs with 9+/-1 weeks of AVB and controls with sinus rhythm. I(TO1) density and kinetics and I(K1) outward current were not different between chronic AVB and control cells. I(Kr) had a similar voltage dependence of activation and time course of deactivation in chronic AVB and control. I(Kr) density was similar in LV myocytes but smaller in RV myocytes (-45%) of chronic AVB versus control. For I(Ks), voltage-dependence of activation and time course of deactivation were similar in chronic AVB and control. However, I(Ks) densities of LV (-50%) and RV (-55%) cells were significantly lower in chronic AVB than control.


CONCLUSIONS
Significant downregulation of delayed rectifier K(+) current occurs in both ventricles of the dog with chronic AVB. Acquired TdP in this animal model with biventricular hypertrophy is thus related to intrinsic repolarization defects.
Volders
P G
PG
Department of Cardiology, Cardiovascular Research Institute Maastricht,Maastricht University, the Netherlands. p.volders@cardio.azm.nl
Sipido
K R
KR
Vos
M A
MA
Spätjens
R L
RL
Leunissen
J D
JD
Carmeliet
E
E
Wellens
H J
HJ
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002908:Chronic Disease; D051668:Delayed Rectifier Potassium Channels; D004198:Disease Susceptibility; D004285:Dogs; D015536:Down-Regulation / Q000502:physiology*; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006327:Heart Block / Q000378:metabolism*; D006352:Heart Ventricles / Q000737:chemistry; D008133:Long QT Syndrome / Q000378:metabolism; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000502:physiology; D009206:Myocardium / Q000737:chemistry; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D016171:Torsades de Pointes / Q000378:metabolism*; D016276:Ventricular Function
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated