Hescheler J, Kameyama M, Trautwein W
Pflugers Arch. 1986 Aug;407(2):182-9. doi: 10.1007/BF00580674.
The mechanism of muscarinic inhibition of the Ca-current (ICa) was studied in ventricular myocytes of guinea pig hearts and the following results were obtained. Acetylcholine (ACh) in concentrations up to 10(-4) M had little effect, if any, on ICa in control cells. ACh reduced the isoprenaline (ISP)-induced increase of ICa. The dose-response-relation (ISP concentration vs. ICa density) was shifted by ACh towards higher ISP concentrations. But both, at low and high ISP concentrations ACh had nor or little effect. ACh was ineffective when ICa was increased by dialysing the cell with catalytic subunit of cAMP-dependent protein kinase or cAMP. ACh reduced ICa enhanced by isobutylmethylxanthine or by forskolin. ACh did not depress ICa when the cell was dialysed with the non-hydrolysable GTP-derivative, GMP-PNP. In this condition the beta-adrenergic enhancement of ICa was also absent. Pertussis toxin, which is known to inhibit the inhibitory transducer protein (Ni), abolished the ACh response. We concluded from these results that ACh depresses ICa by inhibiting, via Ni, the cAMP production.
在豚鼠心脏心室肌细胞中研究了毒蕈碱对钙电流（ICa）的抑制机制，得到以下结果。浓度高达10（-4）M的乙酰胆碱（ACh）对对照细胞中的ICa几乎没有影响（如果有影响的话）。ACh降低了异丙肾上腺素（ISP）诱导的ICa增加。剂量反应关系（ISP浓度与ICa密度）因ACh而向更高的ISP浓度偏移。但在低和高ISP浓度下，ACh均无作用或作用很小。当用cAMP依赖性蛋白激酶或cAMP的催化亚基透析细胞使ICa增加时，ACh无效。ACh降低了由异丁基甲基黄嘌呤或福斯可林增强的ICa。当用不可水解的GTP衍生物鸟苷-5'-（β，γ-亚甲基）三磷酸（GMP-PNP）透析细胞时，ACh不抑制ICa。在这种情况下，β-肾上腺素能对ICa的增强作用也不存在。已知能抑制抑制性转导蛋白（Ni）的百日咳毒素消除了ACh反应。从这些结果我们得出结论，ACh通过经由Ni抑制cAMP产生来降低ICa。
