Mehrke G, Zong X G, Flockerzi V, Hofmann F
Institut für Pharmakologie und Toxikologie, Technischen Universität München, Germany.
J Pharmacol Exp Ther. 1994 Dec;271(3):1483-8.
The effects of Ro 40-5967, a nondihydropyridine Ca++ channel blocker, on low-voltage activated (T-type) and high-voltage activated (L-type) Ca++ channels were compared. L-type barium currents were measured in Chinese hamster ovary cells stably transfected with the alpha 1 subunit of the class Cb Ca++ channel. T-type barium currents were investigated in human medullary thyroid carcinoma cells. The Ba++ currents of human medullary thyroid carcinoma cells were transient, activated at a threshold potential of -50 mV with the maximum at -14 +/- 3.2 mV and blocked by micromolar Ni++. The T- and L-type current inactivated with time constants of 33.4 +/- 4.1 and 416 +/- 26 msec at maximum barium currents, respectively. Ro 40-5967 inhibited reversibly the T- and L-type currents with IC50 values of 2.7 and 18.6 microM, respectively. The inhibition of the L-type current was voltage-dependent, whereas that of the T-type current was not. Ro 40-5967 blocked T-type current already at a holding potential of -100 mV. The different types of block, i.e., voltage-dependent vs. tonic block, may contribute to the pharmacological profile of Ro 40-5967 in intact animals.
比较了非二氢吡啶类钙离子通道阻滞剂Ro 40-5967对低电压激活（T型）和高电压激活（L型）钙离子通道的作用。在稳定转染了Cb类钙离子通道α1亚基的中国仓鼠卵巢细胞中测量L型钡电流。在人甲状腺髓样癌细胞中研究T型钡电流。人甲状腺髓样癌细胞的Ba++电流是瞬时的，在-50 mV的阈值电位激活，最大值在-14±3.2 mV，被微摩尔浓度的Ni++阻断。在最大钡电流时，T型和L型电流分别以33.4±4.1和416±26毫秒的时间常数失活。Ro 40-5967分别以2.7和18.6 microM的IC50值可逆地抑制T型和L型电流。L型电流的抑制是电压依赖性的，而T型电流的抑制不是。Ro 40-5967在-100 mV的钳制电位下就可阻断T型电流。不同类型的阻断，即电压依赖性阻断和强直阻断，可能有助于Ro 40-5967在完整动物中的药理学特征。
