Kinetic differences between synaptic and extrasynaptic GABAA receptors in CA1 pyramidal cells
Kinetic differences between synaptic and extrasynaptic GABAA receptors in CA1 pyramidal cells
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DOI：
10.1523/jneurosci.20-03-00937.2000
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发表时间：
2000-02-01
影响因子：
5.3
通讯作者：
Pearce, RA
中科院分区：
文献类型：
--
作者：
Banks, MI;Pearce, RA
GABA(A)介导的IPSCs通常比切除的斑块中的受体更快地衰退，以响应施加GABA的短暂脉冲。我们研究了CA1锥体神经元这种差异的来源。这些细胞中的IPSCs迅速衰变，加权时间常数tau(衰变)类似于18毫秒(24摄氏度)，而摘除和有核的斑块对短脉冲GABA(2毫秒，1 mm)的衰变速度是慢速的三倍(tau(衰变)，类似于63毫秒)。这种差异不是由突触和外源性递质瞬变之间的差异引起的，因为(1)对于0.6-4毫秒的脉冲，tau(衰减)不依赖于脉冲持续时间，(2)对低浓度的GABA的反应仍然比iPSC慢(tau(衰减)，类似于41毫秒)，以及(3)切除的斑块对突触释放的GABA的反应具有类似于短脉冲反应的衰减时间。这些数据表明，介导突触反应和短暂脉冲反应的受体具有不同的内在特性。然而，突触受体不会因斑块切除过程而改变，因为在有核的斑块中仍然可以记录到快速、自发的IPSCs。钙的升高选择性地调节了对GABA脉冲的斑块反应，而对记录在有核斑块中的IPSCs没有影响，表明存在两个受细胞内第二信使差异调节的受体群体。我们的结论是，CA1锥体细胞中存在两种具有不同动力学特征的受体群体：主宰外源性GABA应用的切除斑块反应的慢突触外受体和产生快速IPSCs的快突触受体。
GABA(A)-mediated IPSCs typically decay more rapidly than receptors in excised patches in response to brief pulses of applied GABA. We have investigated the source of this discrepancy in CA1 pyramidal neurons. IPSCs in these cells decayed rapidly, with a weighted time constant tau(Decay) of similar to 18 msec (24 degrees C), whereas excised and nucleated patch responses to brief pulses of GABA (2 msec, 1 mM) decayed more than three times as slowly (tau(Decay), similar to 63 msec). This discrepancy was not caused by differences between synaptic and exogenous transmitter transients because (1) there was no dependence of tau(Decay) on pulse duration for pulses of 0.6-4 msec, (2) responses to GABA at concentrations as low as 10 mu M were still slower to decay (tau(Decay), similar to 41 msec) than IPSCs, and (3) responses of excised patches to synaptically released GABA had decay times similar to brief pulse responses. These data indicate that the receptors mediating synaptic versus brief pulse responses have different intrinsic properties. However, synaptic receptors were not altered by the patch excision process, because fast, spontaneous IPSCs could still be recorded in nucleated patches. Elevated calcium selectively modulated patch responses to GABA pulses, with no effect on IPSCs recorded in nucleated patches, demonstrating the presence of two receptor populations that are differentially regulated by intracellular second messengers. We conclude that two receptor populations with distinct kinetics coexist in CA1 pyramidal cells: slow extrasynaptic receptors that dominate the responses of excised patches to exogenous GABA applications and fast synaptic receptors that generate rapid IPSCs.