Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells
Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells
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DOI：
10.1152/jn.01107.2010
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发表时间：
2011-07-01
影响因子：
2.5
通讯作者：
Liu, Siqiong June
中科院分区：
文献类型：
--
作者：
Liu, Yu;Savtchouk, Iaroslav;Liu, Siqiong June
Liu Y，Savtchouk I，Acharjee S，Liu SJ.抑制Ca 2+激活的大电导K+通道活性改变小鼠小脑星状细胞突触AMPA受体表型J Neurophysiol 106：144-152，2011.首次发表于2011年5月11日; doi：10.1152/jn.01107.2010.-许多快速尖峰抑制性中间神经元（包括小脑星状细胞）激发短暂动作电位并表达α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）型谷氨酸受体（AMPAR），该受体可渗透Ca 2+且不含GluR 2亚基。在最近的一项研究中，我们发现增加动作电位时程促进星状细胞中GluR 2基因的转录。我们现在已经测试了控制动作电位持续时间的钾通道的激活可以抑制星状细胞突触处含GluR 2的AMPAR表达的预测。我们发现，大电导钙激活钾（BK）通道介导的去极化诱发的非失活钾电流在星状细胞的大比例。BK通道的药理学阻断延长了突触后星状细胞的动作电位时程，并改变了突触AMPAR亚型，从GluR 2缺乏到含GluR 2的Ca 2+不渗透AMPAR。L-型通道阻滞剂消除了与峰电位增宽相关的Ca 2+内流增加，也阻止了BK通道阻滞剂诱导的AMPAR表型转换。因此，阻断BK钾通道延长了动作电位时程，并通过增强小脑星状细胞中的Ca 2+内流来增加突触处含GluR 2受体的表达。
Liu Y, Savtchouk I, Acharjee S, Liu SJ. Inhibition of Ca2+ activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells. J Neurophysiol 106: 144-152, 2011. First published May 11, 2011; doi:10.1152/jn.01107.2010.-Many fast-spiking inhibitory interneurons, including cerebellar stellate cells, fire brief action potentials and express alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)type glutamate receptors (AMPAR) that are permeable to Ca2+ and do not contain the GluR2 subunit. In a recent study, we found that increasing action potential duration promotes GluR2 gene transcription in stellate cells. We have now tested the prediction that activation of potassium channels that control the duration of action potentials can suppress the expression of GluR2-containing AMPARs at stellate cell synapses. We find that large-conductance Ca2+-activated potassium (BK) channels mediate a large proportion of the depolarization-evoked noninactivating potassium current in stellate cells. Pharmacological blockade of BK channels prolonged the action potential duration in postsynaptic stellate cells and altered synaptic AMPAR subtype from GluR2-lacking to GluR2-containing Ca2+-impermeable AMPARs. An L-type channel blocker abolished an increase in Ca2+ entry that was associated with spike broadening and also prevented the BK channel blocker-induced switch in AMPAR phenotype. Thus blocking BK potassium channels prolongs the action potential duration and increases the expression of GluR2-containing receptors at the synapse by enhancing Ca2+ entry in cerebellar stellate cells.