title: Effects of strophanthidin on intracellular calcium concentration in ventricular myocytes of guinea pig.
abstract: 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.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Su-Wen
authors.initials: SW
authors.lastname: Su
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Xu
authors.forename: He-Shan
authors.initials: HS
authors.lastname: Mei
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Qi
authors.forename: Jing-Xiang
authors.initials: JX
authors.lastname: Yin
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Wang
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000331:Aequorin / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D016257:Fura-2 / Q000494:pharmacology / Q000600:supply & distribution; D006168:Guinea Pigs; D009206:Myocardium / Q000473:pathology; D009543:Nifedipine / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013327:Strophanthidin / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D013779:Tetrodotoxin; D000331:Aequorin; D013327:Strophanthidin; D019284:Thapsigargin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2