Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart.
We investigated the mechanism of positive inotropism of electric currents applied during the absolute refractory period. Ten Langendorff-perfused ferret hearts were instrumented to measure isovolumic left ventricular pressure (LVP) and the aequorin luminescence. Biphasic square-wave electric currents (+/-20 mA, total duration 30 ms) were delivered between pairs of electrodes. Six hearts were perfused at different extracellular Ca(2+) concentrations ([Ca(2+)](o); 1, 2, 4, and 8 mM). These signals increased LVP from 50.0 +/- 9.4 to 70.1 +/- 14.7, from 67.5 +/- 11.0 to 79.0 +/- 15.6, from 79.3 +/- 21.0 to 87.1 +/- 22.8, and from 84.6 +/- 24.0 to 91.8 +/- 28.5 mmHg at the respective [Ca(2+)](o) (P < 0.05). Peak free intracellular [Ca(2+)] ([Ca(2+)](i)) increased from 0.52 +/- 0.13 to 1.37 +/- 0.23, from 0.76 +/- 0.23 to 1.73 +/- 0.14, from 1.10 +/- 0.24 to 2.05 +/- 0.33, and from 1.41 +/- 0.36 to 2.24 +/- 0.36 microM/ml, respectively (P < 0.001). With the use of 1 mg/l propranolol with 1 mM [Ca(2+)](o), LVP and [Ca(2+)](i) were increased significantly from 48.7 +/- 8.18 to 56.3 +/- 6.11 mmHg and from 0.61 +/- 0.11 to 1.17 +/- 0.20 microM, respectively (P < 0.05). In conclusion, positive inotropism of such electrical currents was due to increased peak [Ca(2+)](i) and Ca(2+) responsiveness of the myofilaments did not change significantly.
Mohri
Satoshi
S
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Shimizu
Juichiro
J
Mika
Yuval
Y
Shemer
Itzhak
I
Wang
Jie
J
Ben-Haim
Shlomo
S
Burkhoff
Daniel
D
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000331:Aequorin; D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D004553:Electric Conductivity; D005289:Ferrets / Q000502:physiology*; D005456:Fluorescent Dyes; D008163:Luminescent Measurements; D009200:Myocardial Contraction; D009638:Norepinephrine / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D013268:Stimulation, Chemical; D013599:Systole / Q000502:physiology*; D016277:Ventricular Function, Left
D000319:Adrenergic beta-Antagonists; D005456:Fluorescent Dyes; D000331:Aequorin; D011433:Propranolol; D002118:Calcium; D009638:Norepinephrine