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首页> 外文期刊>Journal of Neurophysiology >GABA uptake and heterotransport are impaired in the dentate gyrus of epileptic rats and humans with temporal lobe sclerosis.
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GABA uptake and heterotransport are impaired in the dentate gyrus of epileptic rats and humans with temporal lobe sclerosis.

机译：在癫痫大鼠和颞叶硬化症患者的齿状回中，GABA的吸收和异源运输受到损害。

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In vivo dialysis and in vitro electrophysiological studies suggest that GABA uptake is altered in the dentate gyrus of human temporal lobe epileptics characterized with mesial temporal sclerosis (MTLE). Concordantly, anatomical studies have shown that the pattern of GABA-transporter immunoreactivity is also altered in this region. This decrease in GABA uptake, presumably due to a change in the GABA transporter system, may help preserve inhibitory tone interictally. However, transporter reversal can also occur under several conditions, including elevations in [K(+)]o, which occurs during seizures. Thus GABA transporters could contribute to seizure termination and propagation through heterotransport. To test whether GABA transport is compromised in both the forward (uptake) and reverse (heterotransport) direction in the sclerotic epileptic dentate gyrus, the physiological effects of microapplied GABA and nipecotic acid (NPA; a compound that induces heterotransport) were examined in granule cells in hippocampal slices from kainate (KA)-induced epileptic rats and patients with temporal lobe epilepsy (TLE). GABA- and NPA-induced responses were prolonged in granule cells from epileptic rats versus controls (51.3 and 31.3% increase, respectively) while the conductance change evoked with NPA microapplication was reduced by 40%. Furthermore the ratio of GABA/NPA conductance, but not duration, was significantly >1 in epileptic rats but not controls, suggesting a compromise in transporter function in both directions. Similar changes were observed in tissue resected from epileptic patients with medial temporal sclerosis but not in those without the anatomical changes associated with MTLE. These data suggest that the GABA transporter system is functionally compromised in both the forward and reverse directions in the dentate gyrus of chronically epileptic tissue characterized by mesial temporal sclerosis. This alteration may enhance inhibitory tone interically yet be permissive for seizure propagation due to a decreased probability for GABA heterotransport during seizures.
机译：体内透析和体外电生理研究表明，以颞叶内侧硬化（MTLE）为特征的人颞叶癫痫的齿状回中GABA的摄取发生了改变。相应地，解剖学研究表明，该区域GABA转运蛋白免疫反应性的模式也发生了改变。可能由于GABA转运蛋白系统的变化而导致的GABA吸收下降可能有助于暂时抑制抑制性音调。但是，转运蛋白逆转也可能在几种情况下发生，包括癫痫发作期间[K（+）] o升高。因此，GABA转运蛋白可能有助于癫痫发作的终止和通过异源运输的传播。为了测试在硬化性癫痫性齿状回中正向（摄取）和反向（异向运输）方向上GABA的运输是否受到损害，在颗粒细胞中检查了微施用的GABA和乳酸（NPA;一种诱导异运输的化合物）的生理作用。海藻酸盐（KA）诱发的癫痫大鼠和颞叶癫痫（TLE）患者的海马切片中的这种作用。与对照相比，癫痫大鼠的颗粒细胞中GABA和NPA诱导的反应延长（分别增加51.3％和31.3％），而NPA微量施用引起的电导率变化减少40％。此外，在癫痫大鼠中，GABA / NPA电导率的比率（而非持续时间）显着> 1，而对照则没有，这表明在两个方向上转运蛋白功能均受到损害。在患有内侧颞叶硬化的癫痫患者切除的组织中观察到了类似的变化，但是在没有与MTLE相关的解剖学变化的患者中未观察到类似的变化。这些数据表明，GABA转运蛋白系统在以颞叶硬化为特征的慢性癫痫组织的齿状回中在正向和反向功能上均受到损害。由于癫痫发作期间GABA异源转运的可能性降低，这种改变可能会暂时增强抑制性语调，但允许癫痫传播。

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