1999 Fiscal Year Final Research Report Summary

Physiological and pharmacological study for ATP sensitive K channel in human heart

Research Project

Project/Area Number	10670767
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Pediatrics
Research Institution	Nippon Medical School
Principal Investigator	KATSUBE Yasuhiro Nippon Medical School, Pediatrics, Assistant, 医学部, 助手 (20246523)
Project Period (FY)	1998 – 1999
Keywords	human cardiac cell / ATP sensitive K channel / patch clamp / PDE inhibitor / levosimendan
Research Abstract	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)