Klarsfeld A, Laufer R, Fontaine B, Devillers-Thiéry A, Dubreuil C, Changeux J P
U. R. A. CNRS 0210, Département des Biotechnologies, Institut Pasteur, Paris, France.
Neuron. 1989 Mar;2(3):1229-36. doi: 10.1016/0896-6273(89)90307-3.
Using primary cultures of chicken myotubes, we investigated the involvement of protein kinase C and Ca2+ in the repression of nicotinic acetylcholine receptor (AChR) biosynthesis by electrical activity. Treatment with the Ca2+ channel blocker verapamil or the Na+ channel blocker tetrodotoxin increased alpha subunit mRNA levels 11.5- to 15-fold. The effect of tetrodotoxin was abolished in the presence of the Ca2+ ionophore A23187. Dantrolene, which blocks Ca2+ efflux from the sarcoplasmic reticulum, caused only a 1.7-fold increase in alpha subunit mRNA levels. Down regulation of protein kinase C by prolonged exposure to the phorbol ester TPA or inhibition of protein kinase C by staurosporine led to 8- to 10-fold increases in alpha subunit mRNA levels. Mature and precursor forms of AChR alpha subunit mRNA were found to vary in parallel throughout all of these treatments, suggesting that protein kinase C and Ca2+ ions may modulate AChR alpha subunit biosynthesis at the transcriptional level.
利用鸡肌管的原代培养物，我们研究了蛋白激酶C和Ca2+在电活动对烟碱型乙酰胆碱受体（AChR）生物合成的抑制作用中的参与情况。用Ca2+通道阻滞剂维拉帕米或Na+通道阻滞剂河豚毒素处理可使α亚基mRNA水平提高11.5至15倍。在存在Ca2+离子载体A23187的情况下，河豚毒素的作用被消除。阻断Ca2+从肌浆网流出的丹曲林仅使α亚基mRNA水平提高了1.7倍。通过长时间暴露于佛波酯TPA下调蛋白激酶C或用星形孢菌素抑制蛋白激酶C导致α亚基mRNA水平提高8至10倍。在所有这些处理过程中，发现AChRα亚基mRNA的成熟形式和前体形式平行变化，这表明蛋白激酶C和Ca2+离子可能在转录水平上调节AChRα亚基的生物合成。
