首页> 外文期刊>The European Journal of Neuroscience >Cell-type-specific splicing of KChIP4 mRNA correlates with slower kinetics of A-type current.
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Cell-type-specific splicing of KChIP4 mRNA correlates with slower kinetics of A-type current.

机译:KChIP4 mRNA的细胞类型特异性剪接与A型电流的动力学较慢有关。

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Abstract In neurons, rapidly inactivating A-type potassium currents regulate repetitive firing and sensitivity to synaptic inputs both in the soma and in the dendrites. It has been established that Kv4 family subunits with several modifying proteins such as KChIPs are responsible for A-type current in most neurons. However, it is not clear which of these modifying proteins are responsible for the observed difference in the properties of A-type currents in the neurons. For example, in globus pallidus (GP) and basal forebrain (BF) neurons in rats, A-type current possesses a slowly inactivating (tau > 80 ms) component of inactivation that is absent in the currents obtained from striatal cholinergic interneurons (StrI) and hippocampal area CA1 pyramidal neurons (HIP). It has been shown that KChIP4 splice variant A but not splice variant B can increase inactivation rates of Kv4 current to > 100 ms in Xenopus oocytes. We tested the hypothesis that cell-specific expression of KChIP4A is responsible for the slow inactivation of A-type current in these neurons. Employing single-cell RT-PCR in acutely dissociated rat neurons, KChIP4A mRNA was detected in 12/14 GP cells and in 12/14 BF neurons whereas it was not detected in any StrI or HIP cells. By contrast, the KChIP4 splice variant B was detected in all four types of cells. Moreover, deactivation rates at -100 mV were slower in BF and GP cells than in StrI and HIP neurons as expected, owing to the presence KChIP4A in BF and GP neurons. These data are consistent with our initial hypothesis.
机译:摘要在神经元中,快速失活的A型钾电流调节体细胞和树突中的反复放电和对突触输入的敏感性。已经确定,具有几种修饰蛋白(例如KChIPs)的Kv4家族亚基是大多数神经元中A型电流的原因。然而,尚不清楚这些修饰蛋白中的哪一个负责观察到的神经元A型电流特性的差异。例如,在大鼠的苍白球(GP)和基底前脑(BF)神经元中,A型电流具有缓慢失活(tau> 80 ms)的失活成分,而该电流不存在于纹状体胆碱能中间神经元(StrI)获得的电流中和海马区CA1锥体神经元(HIP)。已经显示,在爪蟾卵母细胞中,KChIP4剪接变体A而不是剪接变体B可以将Kv4电流的失活速率增加至> 100ms。我们测试了KChIP4A的细胞特异性表达导致这些神经元中A型电流缓慢失活的假说。通过在急性分离的大鼠神经元中使用单细胞RT-PCR,在12/14 GP细胞和12/14 BF神经元中检测到KChIP4A mRNA,而在任何StrI或HIP细胞中均未检测到。相比之下,在所有四种类型的细胞中都检测到了KChIP4剪接变体B。此外,由于BF和GP神经元中存在KChIP4A,因此BF和GP细胞在-100 mV时的失活速率比StrI和HIP神经元中的慢。这些数据与我们最初的假设一致。

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