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首页> 外文期刊>Journal of Neurophysiology >Distinct roles of CaMKII and PKA in regulation of firing patterns and K(+) currents in Drosophila neurons.
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Distinct roles of CaMKII and PKA in regulation of firing patterns and K(+) currents in Drosophila neurons.

机译：CaMKII和PKA在果蝇神经元的放电模式和K（+）电流调节中的不同作用。

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The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and the cAMP-dependent protein kinase A (PKA) cascades have been implicated in neural mechanisms underlying learning and memory as supported by mutational analyses of the two enzymes in Drosophila. While there is mounting evidence for their roles in synaptic plasticity, less attention has been directed toward their regulation of neuronal membrane excitability and spike information coding. Here we report genetic and pharmacological analyses of the roles of PKA and CaMKII in the firing patterns and underlying K(+) currents in cultured Drosophila central neurons. Genetic perturbation of the catalytic subunit of PKA (DC0) did not alter the action potential duration but disrupted the frequency coding of spike-train responses to constant current injection in a subpopulation of neurons. In contrast, selective inhibition of CaMKII by the expression of an inhibitory peptide in ala transformants prolonged the spike duration but did not affect the spike frequency coding. Enhanced membrane excitability, indicated by spontaneous bursts of spikes, was observed in CaMKII-inhibited but not in PKA-diminished neurons. In wild-type neurons, the spike train firing patterns were highly reproducible under consistent stimulus conditions. However, disruption of either of these kinase pathways led to variable firing patterns in response to identical current stimuli delivered at a low frequency. Such variability in spike duration and frequency coding may impose problems for precision in signal processing in these protein kinase learning mutants. Pharmacological analyses of mutations that affect specific K(+) channel subunits demonstrated distinct effects of PKA and CaMKII in modulation of the kinetics and amplitude of different K(+) currents. The results suggest that PKA modulates Shaker A-type currents, whereas CaMKII modulates Shal-A type currents plus delayed rectifier Shab currents. Thus differential regulation of K(+) channels may influence the signal handling capability of neurons. This study provides support for the notion that, in addition to synaptic mechanisms, modulations in spike activity patterns may represent an important mechanism for learning and memory that should be explored more fully.
机译：Ca（2 +）/钙调蛋白依赖性蛋白激酶II（CaMKII）和cAMP依赖性蛋白激酶A（PKA）级联与果蝇中这两种酶的突变分析所支持的学习和记忆的神经机制有关。尽管有越来越多的证据表明它们在突触可塑性中的作用，但对它们对神经元膜兴奋性和峰信息编码的调节的关注却较少。在这里我们报告遗传和药理学分析的果蝇中枢神经元的放电模式和潜在的K（+）电流中的PKA和CaMKII的作用。 PKA（DC0）的催化亚基的遗传扰动不会改变动作电位的持续时间，但会破坏神经元亚群中恒定电流注入的穗状反应的频率编码。相反，通过在ala转化子中表达抑制肽来选择性抑制CaMKII延长了刺突持续时间，但不影响刺突频率编码。在CaMKII抑制但未在PKA减少的神经元中观察到增强的膜兴奋性，这是由尖峰的自发爆发指示的。在野生型神经元中，在一致的刺激条件下，尖峰序列的发射方式是高度可再现的。然而，响应于低频递送的相同电流刺激，这些激酶途径中的任一个的破坏导致可变的激发模式。尖峰持续时间和频率编码的这种可变性可能给这些蛋白激酶学习突变体的信号处理精度带来问题。影响特定K（+）通道亚基的突变的药理分析表明，PKA和CaMKII在调制动力学和不同K（+）电流的振幅方面具有独特的作用。结果表明，PKA可以调制Shaker A型电流，而CaMKII可以调制Shal-A型电流以及延迟的整流器Shab电流。因此，K（+）通道的差异调节可能会影响神经元的信号处理能力。这项研究为以下观念提供了支持：除突触机制外，突波活动模式的调节可能代表了学习和记忆的重要机制，应更全面地加以研究。

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