Two different inward rectifier K+ channels are effectors for transmitter-induced slow excitation in brain neurons
Two different inward rectifier K+ channels are effectors for transmitter-induced slow excitation in brain neurons
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DOI：
10.1073/pnas.222379999
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发表时间：
2002-10-29
影响因子：
11.1
通讯作者：
Nakajima, Y
中科院分区：
文献类型：
--
作者：
Bajic, D;Koike, M;Nakajima, Y
P物质（SP）通过抑制内向整流钾通道（Kir）兴奋基底核（NB）的大神经元。研究了NB中的Kir（KirNB）与G蛋白偶联Kir（GIRK）的性质。单通道记录与细胞贴附模式显示组成型激活KirNB通道，这是由SP抑制。当记录方法从细胞内到外的模式改变，KirNB的通道活性保持完整，其组成活性不变。将G β（1 γ 2）应用于由内而外的贴片诱导了第二种Kir（GIRK）的活性。然而，应用Gbeta（1 γ 2）并没有改变KirNB活性。用Galpha（i2）螯合Gbeta（1gamma 2）消除了GIRK活性，而KirNB活性不受影响。KirNB通道的平均开放时间（1.1 ms）与GIRK通道的平均开放时间基本相同。KirNB的单位电导为23 pS（1155 mM [K+]（o）），而GIRK的单位电导更大（32-39 pS）。结果表明，KirNB不同于GIRKs和任何经典的Kirs（IRKs）。全细胞电流记录显示，应用毒蕈碱NB神经元诱导的GIRK电流，这种GIRK电流也被SP抑制。因此，SP抑制KirNB和GIRKs。我们的结论是，兴奋性递质SP有两种类型的Kirs作为其效应器：组成型活性，γ-不依赖的KirNB通道和γ-依赖的GIRK。
Substance P (SP) excites large neurons of the nucleus basalis (NB) by inhibiting an inward rectifier K+ channel (Kir). The properties of the Kir in NB (KirNB) in comparison with the G protein-coupled Kir (GIRK) were investigated. Single-channel recordings with the cell-attached mode showed constitutively active KirNB channels, which were inhibited by SP. When the recording method was changed from the on-cell to the inside-out mode, the channel activity of KirNB remained intact with its constitutive activity unaltered. Application of Gbeta(1gamma2) to inside-out patches induced activity of a second type of Kir (GIRK). Application of Gbeta(1gamma2), however, did not change the KirNB activity. Sequestering Gbeta(1gamma2) with Galpha(i2) abolished the GIRK activity, whereas the KirNB activity was not affected. The mean open time of KirNB channels (1.1 ms) was almost the same as that of GIRKs. The unitary conductance of KirNB was 23 pS (1155 mM [K+](o)), whereas that of the GIRK was larger (32-39 pS). The results indicate that KirNB is different from GIRKs and from any of the classical Kirs (IRKs). Whole-cell current recordings revealed that application of muscarine to NB neurons induced a GIRK current, and this GIRK current was also inhibited by SP. Thus, SP inhibits both KirNB and GIRKs. We conclude that the excitatory transmitter SP has two types of Kirs as its effectors: the constitutively active, Gbetagamma-independent KirNB channel and the Gbetagamma-dependent GIRK.