未成熟大鼠皮层神经元中KCC2的表达足以改变GABA反应的极性。
KCC2 expression in immature rat cortical neurons is sufficient to switch the polarity of GABA responses.
作者信息
Lee Hanmi, Chen Carol Xiu-Qing, Liu Yong-Jian, Aizenman Elias, Kandler Karl
机构信息
Department Neurobiology, University of Pittsburgh School of Medicine, W1447 Biomedical Science Tower, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
出版信息
Eur J Neurosci. 2005 May;21(9):2593-9. doi: 10.1111/j.1460-9568.2005.04084.x.
During brain development, GABA and glycine switch from being depolarizing to being hyperpolarizing neurotransmitters. This conversion results from a gradual decrease in the chloride electrochemical equilibrium potential (ECl) of developing neurons, which correlates to an increase in the expression or activity of the potassium chloride cotransporter, KCC2. However, evidence as to whether KCC2 expression is sufficient, in and of itself, to induce this switch is lacking. In order to address this question, we used a gain-of-function approach by over-expressing human KCC2 (hKCC2) in immature cortical neurons, before endogenous up-regulation of KCC2. We found that premature expression of hKCC2 produced a substantial negative shift in the GABA reversal potential and decreased or abolished GABA-elicited calcium responses in cultured neurons. We conclude that KCC2 expression is not only necessary but is also sufficient for ending the depolarizing period of GABA in developing cortical neurons.
在大脑发育过程中，γ-氨基丁酸（GABA）和甘氨酸从起去极化作用的神经递质转变为起超极化作用的神经递质。这种转变是由于发育中神经元的氯化物电化学平衡电位（ECl）逐渐降低所致，这与氯化钾协同转运蛋白KCC2的表达或活性增加相关。然而，关于KCC2的表达本身是否足以诱导这种转变，目前尚无证据。为了解决这个问题，我们采用了功能获得性方法，在内源性KCC2上调之前，在未成熟的皮质神经元中过表达人KCC2（hKCC2）。我们发现，hKCC2的过早表达使GABA反转电位产生了显著的负向偏移，并降低或消除了培养神经元中GABA引发的钙反应。我们得出结论，KCC2的表达不仅是发育中皮质神经元结束GABA去极化期所必需的，而且也是充分的。
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