title: [The Ca(2+) sensitizers CGP 48506 and EMD 57033, but not the Na(+) channel modulator BDF 9148, prolong relaxation in isolated cardiomyocytes of the guinea pig].
abstract: The sodium channel modulator DPI 201-106 has been described to posses Ca(2+)-sensitizing properties. Therefore, the present study investigated the inotropic effect of the Na(+)-channel modulator BDF 9148 (1 microM), a congener of DPI 201-106, in comparison with the Ca(2+)-sensitizers CGP 48506 (1-50 mumol/l) and EMD 57033 (1-30 mumol/l) in electrically driven left ventricular cardiomyocytes isolated from guinea pigs. The changes of the contraction amplitude in comparison to the basal cell shortening (cell shortening in micron and %) were continuously recorded with a one-dimensional high speed camera. BDF 9148, CGP 48506, and EMD 57033 exerted a significant increase in the contraction amplitude (p < 0.05 vs. control). The maximal positive inotropic effects of CGP 48506 (50 mumol/l) and EMD 57033 (30 mumol/l) were +249 +/- 30% and +226 +/- 28%, respectively. The corresponding value for BDF 9148 (1 mumol/l) was +176 +/- 16%. However, only the Ca(2+)-sensitizers CGP 48506 and EMD 57033, but not BDF 9148, prolonged the contractile twitch. Especially in patients with an already enhanced intracellular myocardial Ca(2+)-concentration, Ca(2+)-sensitizers, which impair relaxation, may be disadvantageous for therapeutical use despite their positive inotropic effect.
authors.affiliation: Labor für Herzmuskelphysiologie und Molekulare Kardiologie Klinik III für Innere Medizin Universität zu Köln Joseph-Stelzmann-Str. 9 50924 Köln, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Brixius
authors.forename: S
authors.initials: S
authors.lastname: Hoischen
authors.forename: C
authors.initials: C
authors.lastname: Zobel
authors.forename: K
authors.initials: K
authors.lastname: Lasek
authors.forename: R H
authors.initials: RH
authors.lastname: Schwinger
mesh_terms: D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D001392:Azocines / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003971:Diastole / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*; D013829:Thiadiazines / Q000494:pharmacology*
chemical_list: D001384:Azetidines; D001392:Azocines; D015220:Calcium Channels; D002316:Cardiotonic Agents; D011804:Quinolines; D015222:Sodium Channels; D013829:Thiadiazines; C070609:EMD 53998; C071117:BDF 9148; C095056:BA 41899