Ansanay H, Dumuis A, Sebben M, Bockaert J, Fagni L
Centre National de la Recherche Scientifique, Unité Propre de Recherche 9023, C.C.I.P.E., Montpellier, France.
Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6635-9. doi: 10.1073/pnas.92.14.6635.
We report the long-term modulation of K+ channels by cAMP in cultured murine colliculi neurons. A short (1-2 s) application of 8-Br-cAMP induced a long-lasting broadening of the action potential, a loss of after-hyperpolarization, and a reduction in spike accommodation. In agreement with these changes, 8-Br-cAMP produced a long-lasting (2 hr) inhibition of a K+ current. These effects were also observed after a short activation of the pituitary adenylyl cyclase-activating polypeptide, beta-adrenergic, and 5-hydroxytryptamine type 4 (5-HT4) receptors, all known to increase cAMP. A transient activation of the cAMP-dependent protein kinase and a long-lasting inhibition of phosphatases (up to 2 hr) were detected. The blockade of the K+ current resulting from a brief application of 8-Br-cAMP or 5-hydroxytryptamine was prolonged from 2 to 4 hr when protein-serine/threonine phosphatases 1 and 2A were inhibited with 10 nM okadaic acid. The critical steps following the cAMP-dependent protein kinase activation and resulting in a long-term blockade of phosphatases are discussed in this report.
我们报道了环磷酸腺苷（cAMP）对培养的小鼠丘脑中神经元钾离子通道的长期调节作用。短暂（1 - 2秒）施加8 - 溴环磷酸腺苷（8 - Br - cAMP）可诱导动作电位长期增宽、后超极化消失以及锋电位适应性降低。与这些变化一致，8 - Br - cAMP对钾离子电流产生了长期（2小时）的抑制作用。在短暂激活垂体腺苷酸环化酶激活多肽、β - 肾上腺素能受体和5 - 羟色胺4型（5 - HT4）受体后也观察到了这些效应，已知这些受体均可增加cAMP。检测到依赖于cAMP的蛋白激酶短暂激活以及磷酸酶的长期抑制（长达2小时）。当用10 nM冈田酸抑制蛋白丝氨酸/苏氨酸磷酸酶1和2A时，由短暂施加8 - Br - cAMP或5 - 羟色胺引起的钾离子电流阻断从2小时延长至4小时。本报告讨论了依赖于cAMP的蛋白激酶激活后导致磷酸酶长期阻断的关键步骤。
