Protein tyrosine kinase involvement in learning-produced changes in Hermissenda type B photoreceptors.

Protein tyrosine kinase involvement in learning-produced changes in Hermissenda type B photoreceptors.
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蛋白酪氨酸激酶参与学习引起的 Hermissenda B 型光感受器变化。

DOI:
10.1152/jn.90732.2008
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发表时间:
2009
影响因子:
2.5
通讯作者:
Farley,Joseph
Farley,Joseph
中科院分区:
医学3区
文献类型:
--
作者:
Jin,Iksung;Huang,Haojiang;Smith,Benjamin;Farley,Joseph

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Hermissenda眼B型光感受器的兴奋性和光反应的学习相关变化由两种不同的K+电流IA和IK-Ca的减少介导。这些K+电流的抑制与条件刺激产生的蛋白激酶C(PKC)的激活有关。是否PKC完全解释兴奋性和K+电流的变化或是否涉及其他激酶的问题很少受到关注。在目前的实验中,我们问蛋白酪氨酸激酶(PTKs)是否也可能有助于条件产生的变化,在B细胞。我们发现,PTK抑制剂染料木黄酮和lavelustin A大大降低了B型细胞的累积去极化,这是联想学习的短期相关性。这种破坏甚至发生在PKC激活被B型细胞预先暴露于佛波酯而被阻断或被假底物抑制肽PKC阻止时[19-31]。PTK抑制剂还增加了电压依赖性K+电流的瞬时(IA)和延迟(IDelayed)成分的幅度,这些成分先前已被证明通过条件反射选择性降低并有助于累积去极化。Genistein部分阻止了由于体外条件反射引起的IA和ID的减少,并阻断了它们的电压依赖性变化。过钒酸根离子电泳,蛋白酪氨酸磷酸酶的有效抑制剂,去极化B型光感受器和闭塞条件产生的累积去极化。过钒酸盐也抑制IA和ID elayed,降低其电压依赖性,并改变失活动力学IA,模仿条件反射。使用磷酸酪氨酸抗体的蛋白质印迹分析表明,调节增加了hermissendaCNS内许多蛋白质的磷酸酪氨酸含量。总的来说,我们的研究结果表明,除了PKC,一个或多个PTKs条件产生的变化中发挥重要作用的B型细胞兴奋性。PTKs和PKC在条件反射过程中会聚以影响B细胞K+电流的减少,显然是通过不同的生物物理机制。
Learning-correlated changes in the excitability and photoresponses of Hermissenda's ocular type B photoreceptors are mediated by reductions in two distinct K+currents,IAandIK-Ca. The suppression of these K+currents has been linked to conditioning-produced activation of protein kinase C (PKC). The question of whether PKC accounts completely for the changes in excitability and K+currents or whether other kinase(s) are involved has received little attention. In the present experiments, we asked whether protein tyrosine kinases (PTKs) might also contribute to conditioning-produced alterations in B cells. We found that the PTK inhibitors genistein and lavendustin A greatly reduced cumulative depolarization of type B cells, a short-term correlate of associative learning. This disruption occurred even when PKC activation had been either occluded by preexposure of type B cells to a phorbol ester or otherwise prevented by the pseudosubstrate inhibitor peptide PKC[19–31]. PTK inhibitors also increased the amplitude of the transient (IA) and delayed (IDelayed) components of voltage-dependent K+current that have previously been shown to be selectively reduced by conditioning and to contribute to cumulative depolarization. Genistein partially prevented the reduction ofIAandIDelayeddue to in vitro conditioning and blocked the changes in their voltage dependencies. Ionophoresis of pervanadate ion, a potent inhibitor of protein tyrosine phosphatases, depolarized type B photoreceptors and occluded conditioning-produced cumulative depolarization. Pervanadate also suppressedIAandIDelayed, reduced their voltage dependence, and altered inactivation kinetics forIA, mimicking conditioning. Western blot analysis using a phosphotyrosine antibody indicated that conditioning increased the phosphotyrosine content of many proteins within theHermissendaCNS. Collectively, our results suggest that in addition to PKC, one or more PTKs play an important role in conditioning-produced changes in type B cell excitability. PTKs and PKCs converge to effect reductions in B cell K+currents during conditioning, apparently through distinct biophysical mechanisms.
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