Wang Wei, Hu Guo-Yuan, Wang Yi-Ping
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu-Chong-Zhi Road, Shanghai 201203, P.R. China.
Life Sci. 2006 May 22;78(26):2989-97. doi: 10.1016/j.lfs.2005.11.024. Epub 2005 Dec 27.
Magnesium lithospermate B (MLB) is the main water-soluble principle of Salviae Miltiorrhizae Radix (also called as 'Danshen' in the traditional Chinese medicine) for the treatment of cardiovascular diseases. MLB was found to possess a variety of pharmacological actions. However, it is unclear whether and how MLB affects the cardiac ion channels. In the present study, the effects of MLB on the voltage-activated ionic currents were investigated in single ventricular myocytes of adult guinea pigs. MLB reversibly inhibited L-type Ca(2+) current (I(Ca,L)). The inhibition was use-dependent and voltage-dependent (the IC(50) value of MLB was 30 microM and 393 microM, respectively, at the holding potential of -50 mV and -100 mV). In the presence of 100 microM MLB, both the activation and steady-state inactivation curves of I(Ca,L) were markedly shifted to hyperpolarizing membrane potentials, whereas the time course of recovery of I(Ca,L) from inactivation was not altered. MLB up to 300 microM had no significant effect on the fast-inactivating Na(+) current (I(Na)), delayed rectifier K(+) current (I(K)) and inward rectifier K(+) current (I(K1)). The results suggest that the voltage-dependent Ca(2+) antagonistic effect of MLB work in concert with its antioxidant action for attenuating heart ischemic injury.
丹酚酸B是丹参治疗心血管疾病的主要水溶性成分。研究发现丹酚酸B具有多种药理作用。然而，丹酚酸B是否以及如何影响心脏离子通道尚不清楚。在本研究中，我们研究了丹酚酸B对成年豚鼠单个心室肌细胞电压激活离子电流的影响。丹酚酸B可逆性抑制L型钙电流（I(Ca,L)）。这种抑制具有使用依赖性和电压依赖性（在-50 mV和-100 mV的钳制电位下，丹酚酸B的IC(50)值分别为30 μM和393 μM）。在100 μM丹酚酸B存在下，I(Ca,L)的激活曲线和稳态失活曲线均显著向超极化膜电位方向移动，而I(Ca,L)从失活状态恢复的时间进程未改变。高达300 μM的丹酚酸B对快速失活钠电流（I(Na)）、延迟整流钾电流（I(K)）和内向整流钾电流（I(K1)）无显著影响。结果表明，丹酚酸B的电压依赖性钙拮抗作用与其抗氧化作用协同发挥，减轻心脏缺血损伤。
