Activity-independent coregulation of IA and Ih in rhythmically active neurons
Activity-independent coregulation of IA and Ih in rhythmically active neurons
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DOI：
10.1152/jn.00281.2005
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发表时间：
2005-11-01
影响因子：
2.5
通讯作者：
Harris-Warrick, RM
中科院分区：
文献类型：
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作者：
MacLean, JN;Zhang, Y;Harris-Warrick, RM
快速瞬态钾或A电流在决定中枢模式产生神经元的活动中起着重要作用。我们之前已经证明，在多刺龙虾的幽门网络神经元中，shal K+通道基因编码I-A。为了进一步研究I-A如何影响幽门神经元和网络活性，我们将一种shal-GFP融合蛋白的RNA微注射到四种已鉴定的幽门神经元类型中。无论细胞类型如何，表达shal-GFP的神经元的I-A振幅都在不断增加。这种I-A的增加与所有幽门神经元中超极化激活的阳离子电流I-h的同时增加是平行的。尽管这些电流显著增加，但仅观察到细胞放电特性的轻微变化。我们使用模型来检验两个假设，以解释这种无法改变发射特性的现象。首先，这可能反映了表达的shal蛋白仅在注射神经元的体细胞和初始神经突上的错误定位，使其在电上远离神经元的整合区。为了验证这一假设，我们建立了一个多室模型，其中I-A的增加可能局限于体细胞、初始神经突或神经细胞/轴突室。尽管与体细胞/初级神经突I-A相比，神经突活性对神经突/轴突I-A的增加更敏感，但与注射了shal- gfp的神经元相比，仅限于体细胞和初级神经突的I-A的增加仍然引起了更剧烈的变化。第二，I-A的增加可以通过内生I-h的增加来补偿。为了验证这一点，我们用循环双细胞模型模拟了I-A和I-h的代偿性增加。我们发现I-h的增加足以补偿I-A增加的影响，前提是它们以恒定的比例增加，正如我们在注射和未注射神经元中实验观察到的那样。因此，在I-A急剧增加的情况下，一种独立于活动的内稳态机制维持了神经元的恒定活动。
The fast transient potassium or A current ( I A) plays an important role in determining the activity of central pattern generator neurons. We have previously shown that the shal K+ channel gene encodes I-A in neurons of the pyloric network in the spiny lobster. To further study how I-A shapes pyloric neuron and network activity, we microinjected RNA for a shal-GFP fusion protein into four identified pyloric neuron types. Neurons expressing shal-GFP had a constant increase in I-A amplitude, regardless of cell type. This increase in I-A was paralleled by a concomitant increase in the hyperpolarization- activated cation current I-h in all pyloric neurons. Despite significant increases in these currents, only modest changes in cell firing properties were observed. We used models to test two hypotheses to explain this failure to change firing properties. First, this may reflect the mislocalization of the expressed shal protein solely to the somata and initial neurites of injected neurons, rendering it electrically remote from the integrating region in the neuropil. To test this hypothesis, we generated a multicompartment model where increases in I-A could be localized to the soma, initial neurite, or neuropil/ axon compartments. Although spike activity was somewhat more sensitive to increases in neuropil/ axon versus somatic/ primary neurite I-A, increases in I-A limited to the soma and primary neurite still evoked much more dramatic changes than were seen in the shal-GFP-injected neurons. Second, the effect of the increased I-A could be compensated by the endogenous increase in I-h. To test this, we modeled the compensatory increases of I-A and I-h with a cycling two-cell model. We found that the increase in I-h was sufficient to compensate the effects of increased I-A, provided that they increase in a constant ratio, as we observed experimentally in both shal-injected and noninjected neurons. Thus an activity- independent homeostatic mechanism maintains constant neuronal activity in the face of dramatic increases in I-A.