Positive inotropic effect of Mg2+ in K+-depolarized isoprenaline-reactivated guinea-pig ventricular strip.
In K+-depolarized isoprenaline-reactivated guinea-pig ventricular strips increase in external Mg2+ concentration produced a biphasic inotropic effect i.e. at low concentrations (2.5-7.5 mM) a slight negative inotropic effect was observed, while at higher Mg2+ concentrations (10-17.5 mM) a strong positive inotropic effect become predominant. Variation in extracellular K+ concentration (17-22 and 25 mM) determined a concentration related reduction in Mg2+-induced positive inotropic effect. Increase in extracellular Ca2+ concentration (2.5-3.6 and 5.4 mM) prevented the development of Mg2+-induced negative inotropic effect but did not affect the magnitude of the positive inotropic effect. Mg2+-induced positive inotropic effect was unaffected by TTX (3 mg/l) and even enhanced by nifedipine (65 nM). Caffeine (0.2-15 mM) antagonized in a concentration dependent manner the positive inotropic effect of Mg2+. On the other hand in the presence of Mg2+ (15 mM) caffeine (0.2 mM) was unable to exert its positive inotropic effect. Mg2+ (15 mM) determined a "Ca2+ entry blocking"--like modifications of electrophysiological parameters of slow action potentials elicited by isoprenaline in K+-depolarized preparations. Such effects of Mg2+ were also present during the positive inotropic effect. The possible mechanisms responsible for these complex inotropic effects of Mg2+ are discussed.
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S
Manzini
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Parlani
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M
Astolfi
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CA
Maggi
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Meli
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology
D002110:Caffeine; D013779:Tetrodotoxin; D008274:Magnesium; D009543:Nifedipine; D007545:Isoproterenol; D011188:Potassium