Kostyuk P G, Lukyanetz E A, Ter-Markosyan A S
A.A. Bogomoletz Institute of Physiology, Ukrainian Academy of Sciences, Kiev.
Pflugers Arch. 1992 Feb;420(2):146-52. doi: 10.1007/BF00374983.
Effects of parathyroid hormone substance (PTH) on the voltage-activated calcium current (ICa) were studied on intracellularly perfused neurones of the snail, Helix pomatia, under voltage-clamp conditions. Application of 0.1 nM PTH produced a marked potentiation of the current. The effect developed slowly (60-70 min) and remained after removal of PTH. Potentiation could be observed in most neurones, but varied considerably from cell to cell; in some neurones ICa was increased 2- to 3-fold. Addition of ethylenebis(oxonitrilo)tetraacetate (EGTA, 10 mM) to, or removal of adenosine 5'-triphosphate (ATP, 2 mM) from the intracellular perfusing solution resulted in a suppression or attenuation of the potentiating effect. The effect could be reproduced by the synthetic 1-34 amino acid fragment of PTH. Extracellularly applied protein kinase-C (PK-C) activator phorbol ester phorbol 12-myristate 13-acetate (PMA, 0.1-10 microM) produced a similar slow increase in ICa (up to 1.5- to 2-fold), while its inactive analogue (4 alpha-phorbol ester) had no effect on ICa. The effects of PTH and PMA were not additive. PK-C inhibitors [1-(5-isoquinoline-sulphonyl)-2-methylpiperazine hydrochloride] (H-7, 100 microM) and staurosporine (100 microM) as well as calcium channel antagonists Cd2+, verapamil, nifedipine and nimodipine depressed the effect of PTH. The chloride channel blocker 4,4'-diisothiocyanato-stilbene-2,2'-disulphonic acid (DIDS, 1 mM) did not affect the potentiating action of PTH. Activation of the adenylate cyclase system also potentiated ICa in some neurones, but this effect had a different time course and was additive to the effect of PTH.2=
在电压钳制条件下，研究了甲状旁腺激素物质（PTH）对苹果蜗牛（Helix pomatia）细胞内灌流神经元电压激活钙电流（ICa）的影响。施加0.1 nM PTH可使电流显著增强。这种效应发展缓慢（60 - 70分钟），且在去除PTH后仍持续存在。大多数神经元均可观察到增强效应，但细胞间差异很大；在一些神经元中，ICa增加了2至3倍。向细胞内灌流溶液中添加乙二胺四乙酸（EGTA，10 mM）或去除腺苷5'-三磷酸（ATP，2 mM）会导致增强效应受到抑制或减弱。PTH的合成1 - 34氨基酸片段可重现该效应。细胞外施加蛋白激酶C（PK - C）激活剂佛波酯佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA，0.1 - 10 microM）可使ICa产生类似的缓慢增加（高达1.5至2倍），而其无活性类似物（4α - 佛波酯）对ICa无影响。PTH和PMA的效应并非相加。PK - C抑制剂[1 - （5 - 异喹啉磺酰基） - 2 - 甲基哌嗪盐酸盐]（H - 7，100 microM）和星形孢菌素（100 microM）以及钙通道拮抗剂Cd2 +、维拉帕米、硝苯地平和尼莫地平可抑制PTH的效应。氯离子通道阻滞剂4,4'-二异硫氰酸根合芪 - 2,2'-二磺酸（DIDS，1 mM）不影响PTH的增强作用。腺苷酸环化酶系统的激活在一些神经元中也可增强ICa，但这种效应具有不同的时间进程，且与PTH的效应相加。
