Effects of strophanthidin on intracellular calcium concentration in ventricular myocytes of guinea pig / 药学学报

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 μmol·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 μmol·L-1). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 μmol·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 μmol·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.