Possible contribution of the sarcoplasmic reticulum Ca(2+) pump function to electrical and mechanical alternans.
We investigated the role of the sarcoplasmic reticulum's (SR) Ca(2+) pump function of the in the mechanism of alternans. We recorded the surface ECG, monophasic action potential (MAP) and left ventricular pressure (LVP) in the canine beating heart. Alternans was induced with an abrupt shortening of the cycle length from 1000 to 350 ms. After the control studies, we administered propranolol or isoproterenol. In the presence of propranolol, we administered milrinone or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In the presence of isoproterenol, we administered thapsigargin. Isoproterenol and milrinone attenuated both the electrical and mechanical alternans. Thapsigargin, a specific SR Ca(2+) pump inhibitor, and propranolol magnified both types of alternans. DIDS, a Ca(2+)-activated Cl(-) current (I(Cl(Ca))) inhibitor, attenuated the MAP alternans without an affect on the LVP alternans. Thus, the delayed intracellular Ca(2+) cycling caused by the impaired SR Ca(2+) pump function might produce electrical and mechanical alternans. beta-adrenergic stimulation eliminated these alternans. The I(Cl(Ca)) contributed to the appearance of the electrical alternans.
Kameyama
Mikihiko
M
First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Hirayama
Yoshiyuki
Y
Saitoh
Hirokazu
H
Maruyama
Mitsunori
M
Atarashi
Hirotsugu
H
Takano
Teruo
T
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D016764:Cell Polarity; D004285:Dogs; D004553:Electric Conductivity; D005260:Female; D006327:Heart Block / Q000378:metabolism* / Q000503:physiopathology*; D016623:Ion Pumps / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D020105:Milrinone / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D016623:Ion Pumps; D019284:Thapsigargin; D011433:Propranolol; D020105:Milrinone; D007545:Isoproterenol; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium