GABA action in immature neocortical neurons directly depends on the availability of ketone bodies
GABA action in immature neocortical neurons directly depends on the availability of ketone bodies
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DOI：
10.1111/j.1471-4159.2009.06230.x
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发表时间：
2009-08-01
影响因子：
4.7
通讯作者：
Zilberter, Yuri
中科院分区：
文献类型：
--
作者：
Rheims, Sylvain;Holmgren, Carl D.;Zilberter, Yuri
在产后早期，哺乳鼠脑的能量代谢在很大程度上依赖于替代葡萄糖的代谢途径，如酮体（KBs）的利用。然而，KBs如何影响神经元兴奋性尚不清楚。利用新皮质锥体细胞中单个NMDA和gaba激活通道的记录，我们分别研究了KBs对gaba诱导的阴离子电流（E-GABA）的静息膜电位（E-m）和逆转电位的影响。我们发现，在出生后发育（P3-P19）期间，如果新皮质脑切片有足够的KBs供应，E-m和E-GABA分别维持在-83和-80 mV的负水平。相反，KB缺陷会导致E-m （> 5 mV）和E-GABA （> 15 mV）的去极化。kb介导的E-GABA的转移主要是由NKCC1共转运体和Cl-/HCO3转运体的相互作用决定的。因此，通过诱导E-m的超极化移位和调节GABA信号模式，KBs可以有效地控制新生儿皮质神经元的兴奋性。
In the early postnatal period, energy metabolism in the suckling rodent brain relies to a large extent on metabolic pathways alternate to glucose such as the utilization of ketone bodies (KBs). However, how KBs affect neuronal excitability is not known. Using recordings of single NMDA and GABA-activated channels in neocortical pyramidal cells we studied the effects of KBs on the resting membrane potential (E-m) and reversal potential of GABA-induced anionic currents (E-GABA), respectively. We show that during postnatal development (P3-P19) if neocortical brain slices are adequately supplied with KBs, E-m and E-GABA are both maintained at negative levels of about -83 and -80 mV, respectively. Conversely, a KB deficiency causes a significant depolarization of both E-m (> 5 mV) and E-GABA (> 15 mV). The KB-mediated shift in E-GABA is largely determined by the interaction of the NKCC1 cotransporter and Cl-/HCO3 transporter(s). Therefore, by inducing a hyperpolarizing shift in E-m and modulating GABA signaling mode, KBs can efficiently control the excitability of neonatal cortical neurons.