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首页> 外文期刊>The Journal of Physiology >Lanthanum-mediated modification of GABAA receptor deactivation, desensitization and inhibitory synaptic currents in rat cerebellar neurons.
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Lanthanum-mediated modification of GABAA receptor deactivation, desensitization and inhibitory synaptic currents in rat cerebellar neurons.

机译：镧介导的大鼠小脑神经元GABAA受体失活，脱敏和抑制突触电流的修饰。

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1. We investigated La3+ effects on recombinant and native gamma-aminobutyric acid A (GABAA) receptors using rapid agonist applications and on inhibitory synaptic currents (IPSCs) in granule and stellate neurons of rat cerebellar slices. 2. Rapid desensitization of currents elicited by 200 ms pulses of 1 mM GABA to small lifted cells transfected with alpha1beta3gamma2 cDNAs was greatly decreased by the coapplication of 100 microM LaCl3. 3. GABA responses were unaffected when coapplication lasted only 2 ms. In contrast, with LaCl3 pre-perfusion, a significant slowing of deactivation in response to 2 ms applications was observed. LaCl3 pre-perfusion also prolonged the duration of responses to 20 mM taurine. 4. Outside-out patches excised from cells transfected with alpha1beta3gamma2 subunit cDNAs were briefly exposed to a saturating concentration of GABA, eliciting a transient activation of single channel currents with a main conductance of 30 pS. Opening and burst durations increased by pre-equilibration of patches with LaCl3. 5. LaCl3 depressed the peak amplitude without affecting the slow deactivation and desensitization of GABA responses in cells transfected with alpha6beta3gamma2 and alpha6beta3delta cDNAs. No significant difference in La3+ modulation of GABA-gated currents was observed between alpha1beta3gamma2 and alpha1beta3delta receptors. 6. The effects of LaCl3 on deactivation and desensitization of GABA responses observed in nucleated patches excised from rat cerebellar granule and stellate neurons were comparable to those in the cells transfected with alpha1beta3gamma2 cDNAs. In addition, La3+ clearly prolonged the spontaneous IPSC time course without changing the amplitude. 7. Our results indicate that La3+ has a dual action on GABA-gated currents: it decreases desensitization and increases channel opening duration. These actions depend on receptor subunit composition and contribute to the prolongation of IPSCs.
机译：1.我们使用快速激动剂研究了La3 +对重组和天然γ-氨基丁酸A（GABAA）受体的影响，以及对大鼠小脑切片的颗粒和星状神经元中抑制性突触电流（IPSC）的影响。 2.通过共同施用100 microM LaCl3，大大降低了200 ms的1 mM GABA脉冲对转染了alpha1beta3gamma2 cDNA的小举升细胞引起的电流的快速脱敏。 3.共施用仅持续2 ms时，GABA反应不受影响。相比之下，使用LaCl3预灌注后，观察到响应2 ms施加的失活显着减慢。 LaCl3预灌流也延长了对20 mM牛磺酸的反应时间。 4.从用alpha1beta3gamma2亚基cDNA转染的细胞中切出的外面向外贴片短暂暴露于饱和浓度的GABA，以30 pS的主电导率短暂激活单通道电流。通过用LaCl3预先平衡贴片，可以增加打开时间和爆发持续时间。 5. LaCl3降低了峰值幅度，而不会影响用alpha6beta3gamma2和alpha6beta3delta cDNA转染的细胞中GABA响应的缓慢失活和脱敏。在alpha1beta3gamma2和alpha1beta3delta受体之间未观察到对GABA门控电流的La3 +调节的显着差异。 6. LaCl3对从大鼠小脑颗粒和星状神经元切下的有核斑块中观察到的GABA反应失活和减敏的作用与转染了alpha1beta3gamma2 cDNA的细胞中的作用相当。此外，La3 +明显延长了IPSC的自发时间，而没有改变幅度。 7.我们的结果表明，La3 +对GABA门控电流具有双重作用：它降低了脱敏作用并增加了通道开放时间。这些作用取决于受体亚基的组成，并有助于IPSC的延长。

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