Cellular mechanisms of paired electrical stimulation in ferret ventricular myocardium: relationship between myocardial force and stimulus interval change |
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Authors: | Judith K Gwathmey |
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Institution: | (1) Charles A. Dana Research Institute, Harvard Medical School, Boston, Mass., USA;(2) Harvard Thorndike Laboratory of Beth Israel Hospital, Department of Medicine, Cardiovascular Division, Harvard Medical School, Boston, Mass., USA;(3) Department of Molecular and Cellular Physiology, Harvard Medical School, Boston, Mass., USA;(4) Beth Israel Hospital, Boston, Mass., USA |
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Abstract: | Summary The subcellular mechanisms of twitch-force potentiation with paired electrical stimulation was studied in ferret ventricular myocardium using the bioluminescent calcium indicator aequorin. It is demonstrated for the first time that interpolation of an extrasystole in a train of conditioned twitches results in a beat-to-beat change in Ca2+]i and force. Steady-state twitch force and Ca
i
2+
were increased with paired stimulation. Increased Ca2+]0 in the setting of paired stimulation resulted in an increase in the amplitude of the postextrasystole and associated Ca2+ transient. Verapamil, a Ca2+ channel antagonist, had the opposite effect of increased Ca2+]0. Postextrasystole potentiation was still present, but diminished in amplitude. These results indicate that postextrasystole potentiation is in part due to a verapamil-depletable store (Ca2+). Postextrasystole potentiation is therefore predominantly dependent on sarcoplasmic reticulum (SR) Ca2+ loading. Ryanodine, an alkaloid which induces Ca2+ leakage from the SR, abolished postextrasystole potentiation; however, in the presence of ryanodine the extrasystole was potentiated. Caffeine, a phosphodiesterase inhibitor which induces SR Ca2+ release and impairs uptake, also abolished postextrasystole potentiation. As with ryanodine there was resultant potentiation of the extrasystole. In the case of caffeine the calcium transient consisted of a second slow component associated with extrasystole twitch potentiation. The results are consistent with sarcolemmal Ca2+ influx playing a role in potentiation of the extrasystole in the presence of an impaired SR. These data indicate that transsarcolemmal Ca2+ influx in the presence of impaired intracellular Ca2+ buffering can directly activate the myofilaments in agreement with reports on human myocardium.Abbreviations C
conditioned stimulus
- ESI
extrasystolic interval
- Lmax
active tension
- PES
postextrasystole
- PESI
postextrasystolic interval
- SR
sarcoplasmic reticulum
- T
test stimulus |
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Keywords: | Aequorin Calcium Sarcoplasmic reticulum Paired stimulation Ferret Mustela putorius furo |
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