Effects of strophanthidin on intracellular calcium concentration in ventricular myocytes of guinea pig.
- Author:
Su-Wen SU
1
;
Yan-Fang XU
;
He-Shan MEI
;
Ya-Juan QI
;
Jing-Xiang YIN
;
Chuan WANG
;
Yong-Jian ZHANG
;
Yong-Li WANG
Author Information
1. Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
- Publication Type:Journal Article
- MeSH:
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester;
pharmacology;
Aequorin;
pharmacology;
Animals;
Calcium;
metabolism;
Calcium Channel Blockers;
pharmacology;
Calcium Channels;
metabolism;
Fura-2;
pharmacology;
supply & distribution;
Guinea Pigs;
Myocardium;
pathology;
Nifedipine;
pharmacology;
Ryanodine;
pharmacology;
Sarcolemma;
metabolism;
pathology;
Sarcoplasmic Reticulum;
drug effects;
metabolism;
Sodium-Calcium Exchanger;
Sodium-Potassium-Exchanging ATPase;
antagonists & inhibitors;
Strophanthidin;
pharmacology;
Tetrodotoxin;
pharmacology;
Thapsigargin;
pharmacology
- From:
Acta Pharmaceutica Sinica
2008;43(3):259-266
- CountryChina
- Language:English
-
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.
