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首页> 外文期刊>The European Journal of Neuroscience >Suppression of a slow post-spike afterhyperpolarization by calcineurin inhibitors.
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Suppression of a slow post-spike afterhyperpolarization by calcineurin inhibitors.

机译：钙调神经磷酸酶抑制剂抑制突波后超极化缓慢。

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Abstract A subset of myenteric neurons in the intestine (AH neurons) generate prolonged (>5 s) post-spike afterhyperpolarizations (slow AHPs) that are insensitive to apamin and tetraethylammonium. Generation of slow AHPs depends critically on Ca(2+) entry and intracellular release of Ca(2+) from stores, which then leads to the activation of a K(+) conductance that underlies the slow AHP (g(sAHP)). Slow AHPs are inhibited by stimulation of the cAMP/protein kinase A (PKA) pathway, suggesting that phosphorylation of the K(+)-channels that mediate the g(sAHP) (K(sAHP)-channels) is responsible for suppression of slow AHPs and possibly for the repolarization phase of slow AHPs. In the present study, we investigated the possibility that the rising phase of the slow AHP is mediated by dephosphorylation of K(sAHP)-channels by calcineurin (CaN), a Ca(2+)-calmodulin-dependent protein phosphatase, leading to an increase in g(sAHP) and activation of the associated current I(sAHP). Slow AHPs and I(sAHP) were recorded using conventional recording techniques, and we tested the actions of two inhibitors of CaN, FK506 and cyclosporin A, and also the effect of the CaN autoinhibitory peptide applied intracellularly, on these events. We report here that all three treatments inhibited the slow AHP and I(sAHP) (>70%) without significantly affecting the ability of neurons to fire action potentials. In addition, the slow AHP and I(sAHP) were suppressed by okadaic acid, an inhibitor of protein phosphatases 1 and 2A. Our results indicate that activation of the g(sAHP) that underlies the post-depolarization slow AHPs in AH neurons is mediated by the actions CaN and non-Ca(2+)-dependent phosphatases.
机译：摘要肠道中的一部分肠系膜神经元（AH神经元）会在穗后超极化（AHP缓慢）后产生延长的（> 5 s），这些时间对芹菜素和四乙铵不敏感。慢速AHP的生成关键取决于Ca（2+）的进入和从存储区中Ca（2+）的细胞内释放，然后导致慢速AHP（g（sAHP））的K（+）电导的激活。缓慢的AHP被cAMP /蛋白激酶A（PKA）通路的刺激所抑制，表明介导g（sAHP）的K（+）通道的磷酸化（K（sAHP）通道）导致了慢速AHP的抑制。 AHP，可能用于慢速AHP的复极化阶段。在本研究中，我们调查了慢的AHP的上升阶段是由钙调神经磷酸酶（CaN）（一种Ca（2 +）-钙调蛋白依赖性蛋白磷酸酶）介导的K（sAHP）通道的去磷酸化介导的可能性。 g（sAHP）的增加和相关电流I（sAHP）的激活。使用常规记录技术记录了慢速AHP和I（sAHP），我们测试了两种CaN抑制剂FK506和环孢菌素A的作用，以及在细胞内施用CaN自抑制肽对这些事件的影响。我们在这里报告，这三种治疗均抑制慢速AHP和I（sAHP）（> 70％），而没有显着影响神经元激发动作电位的能力。另外，冈田酸抑制了慢速AHP和I（sAHP），冈田酸是蛋白磷酸酶1和2A的抑制剂。我们的结果表明，激活AH神经元后去极化慢AHP的g（sAHP）的激活是由CaN和非Ca（2+）依赖性磷酸酶的作用介导的。

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