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Am J Physiol Heart Circ Physiol (November 21, 2002). doi:10.1152/ajpheart.00378.2002
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Articles in PresS, published online ahead of print November 21, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00378.2002
Submitted on May 1, 2002
Accepted on November 13, 2002

Electric Currents Applied during the Refractory Period Enhance Contractility and Systolic Calcium in Ferret

Satoshi Mohri1*, Juichiro Shimizu1, Yuval Mika2, Itzhak Shemer3, Jie Wang1, Shlomo Ben-Haim4, and Daniel Burkhoff1

1 Departments of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA
2 IMPULSE Dynamics, Tirat-Ha' Carmel, Israel
3 Department of Physiology Faculty of Medicine, Technion, Haifa, Israel
4 IMPULSE Dynamics, Tirat-Ha' Carmel, Israel; Department of Physiology Faculty of Medicine, Technion, Haifa, Israel

* To whom correspondence should be addressed. E-mail: smohri{at}md.okayama-u.ac.jp.

We investigated the mechanism of positive inotropism of electric currents applied during the absolute refractory period. Ten Langendorf 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 msec) were delivered between pairs of electrodes. Six hearts were perfused at different extracellular calcium concentrations ([Ca2+]o: 1, 2, 4 and 8mM). 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, from 84.6±24.0 to 91.8±28.5 mmHg at the respective [Ca2+]o (p<0.05). Peak free intracellular calcium concentration ([Ca2+]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 µM/ml, respectively (p<0.001). With 1 mg/L propranolol at 1 mM [Ca2+]o, LVP and [Ca2+]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 µM, respectively (p<0.05). In conclusion, positive inotoropism of such electrical currents was due to increased peak [Ca2+]i and Ca2+ responsiveness of the myofilaments did not change significantly.




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