Tao Jin, Wang Hongyi, Zhou Hong, Li Shengnan
Department of Pharmacology, Nanjing Medical University, Hanzhong Road 140, Nanjing 210029, PR China.
Life Sci. 2005 Oct 28;77(24):3021-30. doi: 10.1016/j.lfs.2005.01.039. Epub 2005 Jun 23.
The saponin monomer 13 of dwarf lilyturf tuber (DT-13), one of the saponin monomers of dwarf lilyturf tuber, has been found to have potent cardioprotective effects. In order to investigate the effects of DT-13 on L-type calcium currents (I(Ca,L)), exploring the mechanisms of DT-13's cardioprotective effects in the condition of pathophysiology, we directly measured the I(Ca,L) during hypoxia in the adult rat cardiac myocytes exposed to DT-13 using standard whole-cell patch-clamp recording technique. Our previous results showed that DT-13 exerted decreasing effects on the I(Ca,L) of the single adult rat cardiac myocytes. In the condition of hypoxia, the current density was inhibited by about 29% after exposure of the cells to DT-13 (0.1 micromol L(-1)) for 10 min, from 6.96+/-1.05 pA/pF to 4.38+/-0.35 pA/pF (n=5, P<0.05). This I(Ca,L)-inhibiting action of DT-13 was concentration-dependent and showed no frequency-dependence. DT-13 up-shifted the current-voltage (I-V) curve. Steady-state activation of I(Ca,L) was not affected markedly, and the half activation potential (V(0.5)) in the presence of DT-13 (0.1 micromol L(-1)) was also not significantly different. DT-13 at 0.1 micromol L(-1) markedly accelerated the voltage-dependent steady-state inactivation of calcium current and shifted the steady-state inactivation curve of I(Ca,L) to the left. In combination with previous reports, these results suggest that there might be a close relationship between the cardioprotective effects of DT-13 and L-type calcium channels in the condition of hypoxia.
麦冬皂苷单体13(DT - 13)是麦冬的皂苷单体之一,已被发现具有强大的心脏保护作用。为了研究DT - 13对L型钙电流(I(Ca,L))的影响,探索DT - 13在病理生理条件下心脏保护作用的机制,我们采用标准的全细胞膜片钳记录技术,直接测量了成年大鼠心肌细胞在缺氧状态下暴露于DT - 13时的I(Ca,L)。我们之前的结果表明,DT - 13对单个成年大鼠心肌细胞的I(Ca,L)有降低作用。在缺氧条件下,细胞暴露于DT - 13(0.1 μmol L(-1))10分钟后,电流密度从6.96±1.05 pA/pF抑制至4.38±0.35 pA/pF(n = 5,P<0.05),约抑制了29%。DT - 13的这种I(Ca,L)抑制作用呈浓度依赖性,且无频率依赖性。DT - 13使电流 - 电压(I - V)曲线向上移位。I(Ca,L)的稳态激活没有明显受到影响,在存在DT - 13(0.1 μmol L(-1))时的半激活电位(V(0.5))也没有显著差异。0.1 μmol L(-1)的DT - 13显著加速了钙电流的电压依赖性稳态失活,并使I(Ca,L)的稳态失活曲线向左移位。结合之前的报道,这些结果表明在缺氧条件下,DT - 13的心脏保护作用与L型钙通道之间可能存在密切关系。