|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1999 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1998 : ¥2,500,000 (Direct Cost : ¥2,500,000)
We had explored the ionic channels of human cardiac cells using whole-cell voltage clamp method. To activate the ionic channels, we used a novel Ca sensitizer, levosimendan, which has the action of opening the ATP sensitive K channel and of phosphodiesterase III inhibition. We studied about the ATP sensitive K channel mainly in 1998, and about the stimulation of L-type Ca channel through phosphodiesterase III inhibition in 1999. We found the following results.
1. Levosimendan is reported to have an action of opening the ATP sensitive K channel in rat ventricular cells and mesenteric artery cells. According to our experiments, levosimendan also has the action of opening the ATP sensitive K channel in human atrial cells.
2. ATP sensitive K channel was not activated in clinically relevant concentration (【approximately equal】nM), gut was activated in more high concentration such as 10 mM. These showed that levosimendan act as a cardioprotective agent by opening ATP sensitive K channels in the pathophysiological conditions such as regional ischemia.
3. Levosimendan stimulated the nifedipine sensitive Ca current (L-type Ca channel) by inhibiting the phosphodiesterase III with ECィイD250ィエD2 value of 56 nM, and maximal effect was 134% of control at 1μM.
These resuls were presented at the following meetings.
1. 15ィイD1thィエD1 Society of Japanese Electrocardiography (1998, 10/1-2, Kagoshima)
2. 35ィイD1thィエD1 Carduikiguca Paediatrica Japonica (1999, 7/7-9, Fukuoka)
3. 21ィイD1stィエD1 European Society of Cardiology (1999, 8/28-9/1, Barcelona, Spain)