Diacylglycerol kinase ζ inhibits Gαq-induced atrial remodeling in transgenic mice

Abstract

BACKGROUND Our previous study demonstrated that diacylglycerol kinase ζ (DGKζ),

Diacylglycerol Kinase ζ Inhibits Ventricular Tachyarrhythmias in a Mouse Model of Heart Failure

“…Interestingly, overexpression of DGKζ in Gαq-TG hearts inhibited PVC and VT. Our previous study demonstrated that DGKζ restored the prolonged QT interval of ECG (ie, APD prolongation) in Gαq-TG mice. 7 Moreover, DGKζ inhibited atrial and ventricular remodeling and rescued Gαq-induced HF. 5, 7 These results suggest that DGKζ overexpression in the hearts expressing Gαq inhibits ventricular arrhythmias, such as PVC and VT through the improvement of ventricular remodeling such as APD prolongation.…”

“…7 Moreover, DGKζ inhibited atrial and ventricular remodeling and rescued Gαq-induced HF. 5, 7 These results suggest that DGKζ overexpression in the hearts expressing Gαq inhibits ventricular arrhythmias, such as PVC and VT through the improvement of ventricular remodeling such as APD prolongation. Moreover, protein kinase C (PKC) activated by DAG potentiates L-type calcium currents, which increase calcium influx through the channels 20 and inhibits potassium channels, such as the delayed rectifier, 21 suggesting calcium overload in myocardium which leads to triggering events.…”

“…After a midline sternal incision, hearts were quickly excised and connected to a modified Langendorff apparatus. 7 Each preparation was perfused under constant flow conditions with oxygenated (95% oxygen, 5% CO2) Tyrode's solution containing in mM: NaCl, 141; KCl, 5; CaCl2, 1.8; NaHCO3, 25; MgSO4, 1; NaH2PO4, 1.2; HEPES, 5; and dextrose, 5 (pH of 7.4 at 36±1°C). Perfusion pressure was measured with a pressure transducer (Nihon Kohden Co, Tokyo, Japan) and maintained within a pressure range (50-60 mmHg) by adjusting flow.…”

“…7 Therefore, we first examined whether VT is induced in Gαq-TG mice and whether DGKζ inhibits the induction of VT. ECG lead II was recorded for 10 min in anesthetized WT (n=14), Gαq-TG (n=14), and Gαq/DGKζ-TG (n=14) mice. Shown in Figure 1A are representative ECG recorded.…”

“…6 Moreover, we recently demonstrated that DGKζ inhibits atrial structural remodeling and atrial fibrillation in Gαq-TG mice. 7 However, whether VT is induced in Gαq-TG mice and DGKζ can inhibit VT are still unknown. The first objective of this study was to elucidate effects of DGKζ on the VT using the Gαq-TG mouse 6 and a double transgenic mouse with cardiac-specific overexpression of both DAG kinase (DGK) ζ and the activated Gαq (Gαq/ DGKζ-TG).…”