| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
|
|---|
| Research Abstract |
This project was carried out to characterize the background K^+ current in cardiac myocytes, particularly in pacemaker cells of sinoatrial node in relation to its possible contribution to the pacemaker activity. The following results were obtained.
1)Species and regional heterogeneity of background K^+ current.
In rat atrial cells, the background K^+ current was increased by increasing external pH, and inhibited by bupivacaine or metanandamide. In addition, the K^+ current was enhanced by halothane. All these properties were similar to TASK, a member of 4 TM K^+ channels. Thus, TASK may play a role for repolarization of rat atrial myocytes. On the other hand, the background K^+ current in rabbit sinoatrial node (SAN) cells was insensitive to metanandamide, and was inhibited by 4-aminopyridine. In porcine SAN cells, the background current was significantly smaller than that of rabbit. These findings indicate that the difference in the current density of the K^+ current contributes to different firing frequency among various mammalian species.
2)Action potential of porcine sinoatrial node cells.
The action potential (AP) duration of porcine SAN cells is significantly longer than that of rabbit, leading to slower heart rate in pigs. We have shown that, in addition to the lack of the background K^+ current, window component of the L-type Ca^<2+> current helps to prolong the AP duration. The L-type Ca^<2+> channel in SAN cells is kinetically and biologically different from that of ventricular cells.
3)Effects of inhalational anesthetics on delayer rectifier K^+ current
Sevoflurane, a most popular inhalational anesthetics in Japan, activates the background K^+ current. Also the anesthetics is shown to inhibit the slowly activating delayed rectifier K^+ current. The inhibition occurs at clinically relevant concentrations. The resulting prolongation of ventricular repolarization may partly account for the clinical observation of excessive QT prolongation by these anesthetics.
|
