The effects of electrotonic interaction on M cell.

Research Project

Project/Area Number	13670749
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Circulatory organs internal medicine
Research Institution	Nippon Medical School
Principal Investigator	HIRAYAMA Yoshiyuki Nippon Medical School, Department of Medicine, Research Assistant, 医学部, 助手 (50322516)
Project Period (FY)	2001 – 2002
Project Status	Completed (Fiscal Year 2002)
Budget Amount *help	¥2,100,000 (Direct Cost: ¥2,100,000) Fiscal Year 2002: ¥100,000 (Direct Cost: ¥100,000) Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords	Ca^<2+> / heart / ventricular myocyte / alternans / arrhythmia / 心筋 / M細胞 / gap junction / 不整脈
Research Abstract	Background Despite growing empiric evidence that T wave alternans is an important clinical measure to predict cardiac electrical instability, its exact mechanism remains controversial. We have proposed that delayed intracellular Ca^<2+> cycling can be the common cause of electrical and mechanical alternans. To confirm this hypothesis and extend our understanding, we investigated the roles of Ca^<2+> pump function of the sarcoplasmic reticulum (SR) in the mechanism of alternans. Methods and Results We recorded surface ECG, monophasic action potential (MAP) using suction electrode and left ventricular pressure (LVP) in canine beating heart. The time constant of LVP decay (τ) was calculated at a basic cycle length of 1000 msec to speculate Ca^<2+> pump function of SR. Alternans was induced with an abrupt shortening of the cycle length to 350 msec. The magnitude of MAP or LVP alternans was defined as the difference in the MAP duration at 30% repolarization or in LVP between the 30th and 31st paced beats. Isoproterenol or milrinone reduced τ and significantly attenuated the magnitudes of both MAP and LVP alternans. Thapsigargine or propranolol increased τ and enhanced the magnitudes of these alternans. 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of Ca^<2+> activated Cl^- current (I_<Cl(Ca)>), attenuated the magnitude of MAP alternans without affecting LVP alternans. Conclusions Delayed intracellular Ca^<2+> cycling caused by impaired Ca^<2+> pump function produced electrical and mechanical alternas. β-adrenergic stimulation accelerated Ca^<2+> pump function and eliminated these alternans. I_<Cl(Ca)> played an important role in the occurrence of electrical alternans.