| First Author | Hirose M | Year | 2011 |
| Journal | Circ J | Volume | 75 |
| Issue | 10 | Pages | 2333-42 |
| PubMed ID | 21778596 | Mgi Jnum | J:343083 |
| Mgi Id | MGI:7562617 | Doi | 10.1253/circj.cj-10-1213 |
| Citation | Hirose M, et al. (2011) Diacylglycerol kinase zeta inhibits ventricular tachyarrhythmias in a mouse model of heart failure. Circ J 75(10):2333-42 |
| abstractText | BACKGROUND: Diacylglycerol kinase zeta (DGKzeta) inhibited atrial tachyarrhythmias in a mouse model of heart failure (HF) in our study. However, whether DGKzeta prevents the HF-induced ventricular tachyarrhythmia (VT) is unknown. METHODS AND RESULTS: Effects of DGKzeta on VT using transgenic mice with transient cardiac expression of activated G protein alpha(q) (Galpha(q)-TG; model of HF) were elucidated and double transgenic mice with cardiac-specific overexpression of both DGKzeta and the activated Galpha(q) (Galpha(q)/DGKzeta-TG) were used. Premature ventricular contraction (PVC) and/or VT were frequently observed in Galpha(q)-TG mice but not in Galpha(q)/DGKzeta-TG and wild-type (WT) mice (P<0.01). Protein expressions of canonical transient receptor potential (TRPC) channels 3 and 6 increased in Galpha(q)-TG hearts compared with WT and Galpha(q)/DGKzeta-TG hearts. SK&F96365, a TRPC channel blocker, decreased the number of PVC and prevented VT in anesthetized Galpha(q)-TG mice (P<0.05). 1-oleoyl-2-acyl-sn-glycerol (OAG), a diacylglycerol analogue, increased the number of PVC in isolated Galpha(q)-TG hearts compared with WT hearts and induced VT in Galpha(q)-TG hearts (P<0.01). SK&F96365 decreased the number of PVC and prevented VT in isolated Galpha(q)-TG hearts (P<0.01) even in the presence of OAG. Early afterdepolarization (EAD)-induced triggered activity was frequently observed in single Galpha(q)-TG ventricular myocytes. Moreover, SK&F96365 prevented the EAD. CONCLUSIONS: These results demonstrated that DGKzeta inhibited VT in a mouse model of HF and suggest that TRPC channels participate in VT induction in failing hearts. |
