title: Pimobendan directly sensitizes reconstituted thin filament to slide on cardiac myosin.
abstract: To elucidate the mechanism of the Ca(2+)-sensitizing action of pimobendan, cardiac thin filaments were reconstituted from actin and tropomyosin-troponin complex and made to slide on a myosin layer. Although filaments showed Brownian movement with a low Ca2+ concentration, they slid at a constant velocity above a certain level of Ca2+ concentration, showing that the sliding was regulated by Ca2+ within a narrow pCa range. Acidosis, addition of inorganic phosphate, and phosphorylation of troponin I increased the threshold Ca2+ concentration. Addition of pimobendan reversed these desensitization effects. These results clearly demonstrated that pimobendan directly increases the Ca2+ sensitivity of thin filament.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sata
authors.forename: S
authors.initials: S
authors.lastname: Sugiura
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Aoyagi
authors.forename: S
authors.initials: S
authors.lastname: Momomura
authors.forename: T
authors.initials: T
authors.lastname: Serizawa
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D008297:Male; D009218:Myosins / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; D009218:Myosins; D002118:Calcium