Inhibitory Effect of Vascular Endothelial Growth Factor on the Slowly Activating Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes.
J Am Heart Assoc
; 7(3)2018 01 26.
Article
en En
| MEDLINE
| ID: mdl-29374044
ABSTRACT
BACKGROUND:
Vascular endothelial growth factor (VEGF) exerts a number of beneficial effects on ischemic myocardium via its angiogenic properties. However, little is known about whether VEGF has a direct effect on the electrical properties of cardiomyocytes. In the present study, we investigated the effects of different concentrations of VEGF on delayed rectifier potassium currents (IK) in guinea pig ventricular myocytes and their effects on action potential (AP) parameters. METHODS ANDRESULTS:
IK and AP were recorded by the whole-cell patch clamp method in ventricular myocytes. Cells were superfused with control solution or solution containing VEGF at different concentrations for 10 minutes before recording. Some ventricular myocytes were pretreated with a phosphatidylinositol 3-kinase inhibitor for 1 hour before the addition of VEGF. We found that VEGF inhibited the slowly activating delayed rectifier potassium current (IKs) in a concentration-dependent manner (18.13±1.04 versus 12.73±0.34, n=5, P=0.001; 12.73±0.34 versus 9.05±1.20, n=5, P=0.036) and prolonged AP duration (894.5±36.92 versus 746.3±33.71, n=5, P=0.021). Wortmannin, a phosphatidylinositol 3-kinase inhibitor, eliminated these VEGF-induced effects. VEGF had no significant effect on the rapidly activating delayed rectifier potassium current (IKr), resting membrane potential, AP amplitude, or maximal velocity of depolarization.CONCLUSIONS:
VEGF inhibited IKs in a concentration-dependent manner through a phosphatidylinositol 3-kinase-mediated signaling pathway, leading to AP prolongation. The results indicate a promising therapeutic potential of VEGF in prevention of ventricular tachyarrhythmias under conditions of high sympathetic activity and ischemia.Palabras clave
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MEDLINE
Asunto principal:
Canales de Potasio con Entrada de Voltaje
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Bloqueadores de los Canales de Potasio
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Miocitos Cardíacos
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Factor A de Crecimiento Endotelial Vascular
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Ventrículos Cardíacos
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Antiarrítmicos
Idioma:
En
Revista:
J Am Heart Assoc
Año:
2018
Tipo del documento:
Article