1.Effects of strophanthidin on intracellular calcium concentration in ventricular myocytes of guinea pig.
Su-Wen SU ; Yan-Fang XU ; He-Shan MEI ; Ya-Juan QI ; Jing-Xiang YIN ; Chuan WANG ; Yong-Jian ZHANG ; Yong-Li WANG
Acta Pharmaceutica Sinica 2008;43(3):259-266
Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i) was investigated on isolated ventricular myocytes of guinea pig. Single ventricular myocytes were obtained by enzymatic dissociation technique. Fluorescent signal of [Ca2+]i was detected with confocal microscopy after incubation of cardiomycytes in Tyrode' s solution with Fluo3-AM. The result showed that Str increased [Ca2+]i in a concentration-dependent manner. The ventricular myocytes began to round-up into a contracture state once the peak level of [Ca2+]i was achieved in the presence of Str (10 micromol L(- 1)), but remained no change in the presence of Str (1 and 100 nmol L(-1)). Tetrodotoxin (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str (1 and 100 nmol L(-1)) , but had no obvious effects on the action of Str (10 micromol L(-1)). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 micromol L(-1)) or the removal of Ca2+ from Tyrode's solution. In Na+, K+ -free Tyrode' s solution, the response of cardiomycytes in [Ca2+]i elevation to Str (10 micromol L(-1)) was attenuated, while remained no change to Str (1 and 100 nmol L(-1)). TTX, nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str at all of the detected concentrations in Na+, K+ -free Tyrode's solution. The study suggests that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is partially mediated by the extracellular calcium influx through Ca2+ channel or a "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at high (micromolar) concentrations was mainly due to the inhibition of Na+, K+ -ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
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pharmacology
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Aequorin
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pharmacology
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Animals
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Calcium
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metabolism
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Calcium Channel Blockers
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pharmacology
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Calcium Channels
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metabolism
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Fura-2
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pharmacology
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supply & distribution
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Guinea Pigs
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Myocardium
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pathology
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Nifedipine
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pharmacology
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Ryanodine
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pharmacology
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Sarcolemma
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metabolism
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pathology
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Sarcoplasmic Reticulum
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drug effects
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metabolism
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Sodium-Calcium Exchanger
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Sodium-Potassium-Exchanging ATPase
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antagonists & inhibitors
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Strophanthidin
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pharmacology
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Tetrodotoxin
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pharmacology
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Thapsigargin
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pharmacology