Presynaptic Ca2+-activated K+ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release
Presynaptic Ca2+-activated K+ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release
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DOI：
10.1523/jneurosci.21-24-09585.2001
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发表时间：
2001-12-15
影响因子：
5.3
通讯作者：
Storm, JF
中科院分区：
文献类型：
--
作者：
Hu, H;Shao, LR;Storm, JF
大电导Ca 2+激活的K+通道（BK，也称为Maxi-K或Slo通道）广泛存在于脊椎动物神经系统中，但其在哺乳动物脑中突触传递中的功能作用在很大程度上是未知的。结合电生理学和免疫金细胞化学，我们证明存在的功能BK通道在突触前末梢在海马和比较它们的功能作用的CA 3锥体细胞的胞体和终端。BK通道和谷氨酸受体抗体的双标记免疫金分析表明，BK通道靶向放射层Schaffer侧支末端面向突触间隙的突触前膜。CA 1锥体细胞的全细胞、细胞内和场电位记录表明，突触前BK通道被钙内流激活，并可促进突触前动作电位（AP）的复极化和负反馈控制Ca 2+内流和递质释放。这在4-氨基吡啶（4-AP，40-100 μ M）的存在下观察到，其扩大了突触前复合动作电位。相反，在基础实验条件下，突触前BK通道对动作电位或递质释放的调节没有显著贡献，即，没有4-AP，即使在高刺激频率下。这与母细胞体（CA 3锥体细胞）中的情况不同，在母细胞体中BK通道对动作电位复极化有很大贡献。这些结果表明，BK通道的功能作用取决于它们的亚细胞定位。
Large-conductance Ca2+-activated K+ channels (BK, also called Maxi-K or Slo channels) are widespread in the vertebrate nervous system, but their functional roles in synaptic transmission in the mammalian brain are largely unknown. By combining electrophysiology and immunogold cytochemistry, we demonstrate the existence of functional BK channels in presynaptic terminals in the hippocampus and compare their functional roles in somata and terminals of CA3 pyramidal cells. Double-labeling immunogold analysis with BK channel and glutamate receptor antibodies indicated that BK channels are targeted to the presynaptic membrane facing the synaptic cleft in terminals of Schaffer collaterals in stratum radiatum. Whole-cell, intracellular, and field-potential recordings from CA1 pyramidal cells showed that the presynaptic BK channels are activated by calcium influx and can contribute to repolarization of the presynaptic action potential (AP) and negative feedback control of Ca2+ influx and transmitter release. This was observed in the presence of 4-aminopyridine (4-AP, 40-100 muM), which broadened the presynaptic compound action potential. In contrast, the presynaptic BK channels did not contribute significantly to regulation of action potentials or transmitter release under basal experimental conditions, i.e., without 4-AP, even at high stimulation frequencies. This is unlike the situation in the parent cell bodies (CA3 pyramidal cells), where BK channels contribute strongly to action potential repolarization. These results indicate that the functional role of BK channels depends on their subcellular localization.