The action of strophanthidin on calcium-activated current and contraction in single guinea-pig ventricular myocytes.
Calcium-activated tail current was used as a qualitative indicator of changes in [Ca]i in order to investigate the mechanism of strophanthidin-induced inotropy in single guinea-pig ventricular myocytes. Action potentials were interrupted (by application of a voltage clamp to -40 mV) in order to evoke Ca-activated current. Exposure to 10 microM-strophanthidin for 2 min resulted in an increase in contractions associated with complete action potentials and in an increase in Ca-activated current. Strophanthidin appeared not to substantially modify the time course of the envelope of tail currents (recorded by interrupting action potentials at different durations), which is thought to reflect the time course of the systolic [Ca]i transient. Exposure to 1 microM-ryanodine slowed the development of the Ca-activated current envelopes and abolished the above effects of strophanthidin. Exposure to strophanthidin led to reduction in Ca current in a majority of cells (measured by a voltage-clamp step from -40 to 0 mV). These results are consistent with the hypothesis that in single guinea-pig ventricular myocytes strophanthidin causes an increased loading of ryanodine-sensitive intracellular stores of Ca, possibly through reduced extrusion of Ca from the cell by Na-Ca exchange during the action potential plateau.
White
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University Department of Pharmacology, Oxford.
Terrar
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DA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D012433:Ryanodine / Q000494:pharmacology; D013327:Strophanthidin / Q000494:pharmacology*
D012433:Ryanodine; D013327:Strophanthidin; D002118:Calcium