| First Author | Watanabe Y | Year | 2017 |
| Journal | J Pharmacol Sci | Volume | 135 |
| Issue | 1 | Pages | 37-43 |
| PubMed ID | 28928055 | Mgi Jnum | J:287787 |
| Mgi Id | MGI:6363385 | Doi | 10.1016/j.jphs.2017.08.009 |
| Citation | Watanabe Y, et al. (2017) Electrophysiological analyses of transgenic mice overexpressing KCNJ8 with S422L mutation in cardiomyocytes. J Pharmacol Sci 135(1):37-43 |
| abstractText | Genetic analysis of KCNJ8 has pointed a mutation (S422L) as a susceptible link to J wave syndrome (JWS). In vitro expression study indicated that the ATP-sensitive K(+) (KATP) channel with the S422L mutation has the gain-of-function with reduced sensitivity to ATP. However, the electrophysiological impact of KCNJ8 has not been elucidated in vivo. Transgenic mouse strains overexpressing KCNJ8 S422L variant (TGmt) or WT (TGWT) in cardiomyocytes have been created to investigate the influence of KCNJ8 in cardiomyocytes and the JWS-related feature of the S422L variant on the cardiac electrophysiology. These TG strains demonstrated distinct changes in the J-ST segment of ECG with marked QT prolongation, which might be ascribed to the action potential prolongation resulting from the reduction of voltage-dependent K(+) currents in ventricular cells. The pinacidil-induced KATP current was decreased in these TG myocytes and no obvious difference between TG and non-TG (WT) myocytes in the ATP sensitivity of the KATP channel was observed although the open probability of the KATP channels was significantly lower in TG myocytes than WT. These transgenic mouse strains with distinct ECG changes suggested that the S422L mutation in KCNJ8 gene is not a direct cause of JWS. |
