J. Szegi

Effect of dantrolene sodium on the transmembrane potentials and contractility of guinea pig atrial myocardium.

Dantrolene sodium (3 X 10(-4) M) exerted a biphasic effect on the mechanical and electrical activity of the isolated guinea pig left atrium. In the first phase, the drug increased the contractile force by about 200%, and prolonged the action potential duration. This transient positive inotropic effect was antagonized by D-600, a slow Ca2+ channel inhibitor. In the later phase, the drug gradually decreased the amplitude of contractions, shortened the action potential duration and induced contracture. Dantrolene sodium increased the rate of depolarization and overshoot of Ca2+ -mediated slow action potentials. The results suggest that dantrolene sodium increases the slow inward Ca2+ current, causing a positive inotropic effect in the atrial myocardium. The late negative inotropic effect of the drug could be due to a secondary inhibition of the slow inward Ca2+ current due to an increased intracellular free Ca2+ concentration as a consequence of other actions of the drug.

Inhibition of myocardial K+ channels by bromobenzoyl-methyladamantylamine, an adamantane derivative

The effect of bromobenzoyl-methyladamantylamine (BMA) on transmembrane potentials and contractility of atrial and ventricular myocardium of guinea-pig and cat, as well as on transmembrane ionic currents of the frog atrial trabeculae was studied using conventional glass microelectrode and double sucrose-gap voltage clamp techniques. BMA markedly prolonged the action potential duration, depolarized the cell membrane, reduced the rate of rise of the action potential and exerted a positive inotropic effect on non-clamped myocardial preparations. The drug-induced pacemaker activity in ventricular working muscle of cat. Moreover, BMA antagonized the effects of the K+ channel activator acetylcholine in a dose-dependent manner. BMA was found to induce slow response action potentials in K+ -depolarized ventricular myocardium of guinea-pig. In voltage clamp experiments, BMA reduced the outward K+ current but had no effect on either rapid inward Na+ or slow inward Ca2+ currents. The results suggest that BMA is capable of selectively blocking the myocardial K+ channels.

Antagonism between adenosine and bromobenzoyl-methyladamantylamine, A K+ channel blocker, in atrial myocardium of guinea pig

The effect of bromobenzoyl-methyladamantylamine (BMA) on the adenosine-induced changes in the electrical and mechanical activity of the atrial muscle, and the effect of adenosine on the slow action potentials induced by BMA in K+-depolarized atrial myocardium of guinea pig were studied. BMA was able to antagonize the adenosine-induced shortening of the action potential duration and negative inotropic effect. This action of BMA was potentiated by theophylline, and reduced by dipyridamole. Adenosine depressed the BMA-induced slow action potentials. The results suggest that there may be an antagonism between BMA and adenosine.

Action of dimethindene on the electrophysiological and mechanical properties of atrial and ventricular myocardium of guinea-pig.

The effect of dimethindene (DMI) on transmembrane potentials and contractile force was studied in atrial and ventricular myocardium of guinea-pigs. DMI reduced the maximum rate of depolarization (Vmax) without changing the resting potential in both preparations. In ventricular myocardium, DMI shortened the action potential duration and exerted a negative inotropic effect. In atrial muscle, the drug prolonged the action potential duration and induced a positive inotropic effect which could be antagonized with neither the alpha-blocker phentolamine, nor the beta-blocker pindolol, H1-blocker mepyramine and H2-blocker cimetidine. DMI had no effect on the slow action potentials induced by caffeine in K+-depolarized myocardial preparations. The drug consistently shifted the sodium inactivation curve to more negative membrane potentials. The results suggest that DMI has a quinidine-like membrane-stabilizing property, which may be due to its fast Na+ channel blocking activity. The differential inotropic action of the drug in atrial and ventricular myocardium is discussed.

Effect of dimethindene, an antihistaminic drug, on the transmembrane potentials of mammalian myocardium.

Dimethindene (DMI) decreased the maximum rate of rise of action potential (AP) without changing the resting potential in cat ventricular myocardium. DMI abolished the histamine-induced slow APs in left atria but not in right ventricular papillary muscles of guinea-pig, suggesting that DMI blocked the histamine H1-receptors.

Immunofluorescent studies in isoproterenol-induced myocardial necrosis in rats.

Immunofluoreszenz-Nachweis von Myokard-Antikörpern nach Isoproterenol-induzierter Myokardnekrose bei der Ratte in 90% der Tiere.