Somatostatin increases a voltage-insensitive K+ conductance in rat CA1 hippocampal neurons.
Somatostatin increases a voltage-insensitive K+ conductance in rat CA1 hippocampal neurons.
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DOI：
10.1152/jn.1998.79.3.1230
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发表时间：
1998-03
影响因子：
2.5
通讯作者：
P. Schweitzer;S. Madamba;G. Siggins
中科院分区：
文献类型：
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作者：
P. Schweitzer;S. Madamba;G. Siggins
生长抑素 (SST) 是一种参与多个中枢过程的神经肽。在海马体中，SST 使 CA1 锥体神经元超极化并增强 K+ M 电流 (IM)。然而，IM 在这些细胞的静息电位中的参与有限，表明该肽还可能调节另一个通道以使海马锥体神经元 (HPN) 超极化。我们研究了切片制剂中 SST 对大鼠 CA1 HPN 的非失活电导的影响。使用 MK886（一种酶促途径的特异性抑制剂，通过 SST 增强 IM），我们发现并表征了由肽激活的第二电导。当与 MK886 一起使用时，SST 不会影响 IM 或超极化后缓慢的 Ca2+ 依赖性 K+ 电流和阳离子 Q 电流的幅度，但仍然引起外向电流，表明 SST 作用于另一种电导。在 MK886 存在的情况下，SST 引发反向电流约 -100 mV，并显示出线性电流-电压关系。在不同外部 K+ 浓度下获得的反转电位与仅由 K+ 离子携带的电导一致。电流-电压关系的斜率随细胞外 K+ 浓度成比例增加并保持线性。这表明 SST 在 HPN 中打开电压不敏感的漏电流 (IK(L))，而不是其他神经元类型中报道的内向整流 K+ 电流。低浓度的细胞外 Ba2+ (150 M) 仅以与电压无关的方式轻微降低 SST 诱导的效应，而高浓度的 Ba2+ (2 mM) 则完全阻止它。细胞外 Cs+ (2 mM) 不影响外向 SST 电流，但抑制向内分量。我们得出结论，SST 通过激活两种不同的 K+ 电导来抑制 HPN：电压不敏感的 IK(L) 和电压依赖的 IM。 SST 在静息膜电位下的超极化效应似乎主要由 IK(L) 承担，而 IM 在轻微去极化电位下占主导地位。
Somatostatin (SST) is a neuropeptide involved in several central processes. In hippocampus, SST hyperpolarizes CA1 pyramidal neurons and augments the K+ M current (IM). However, the limited involvement of IM at resting potential in these cells suggests that the peptide also may modulate another channel to hyperpolarize hippocampal pyramidal neurons (HPNs). We studied the effect of SST on noninactivating conductances of rat CA1 HPNs in a slice preparation. Using MK886, a specific inhibitor of the enzymatic pathway that leads to the augmentation of IM by SST, we have uncovered and characterized a second conductance activated by the peptide. SST did not affect IM when applied with MK886 or the amplitudes of the slow Ca2+-dependent K+ afterhyperpolarization-current and the cationic Q current but still caused an outward current, indicating that SST acts upon another conductance. In the presence of MK886, SST elicited an outward current that reversed around -100 mV and that displayed a linear current-voltage relationship. Reversal potentials obtained in different external K+ concentrations are consistent with a conductance carried solely by K+ ions. The slope of the current-voltage relationship increased proportionately with the extracellular K+ concentration and remained linear. This suggests that SST opens a voltage-insensitive leak current (IK(L)) in HPNs not an inwardly rectifying K+ current as reported in other neuron types. A low concentration of extracellular Ba2+ (150 M) only slightly decreased the SST-induced effect in a voltage-independent manner, whereas a high concentration of Ba2+ (2 mM) completely blocked it. Extracellular Cs+ (2 mM) did not affect the outward SST current but inhibited the inward component. We conclude that SST inhibits HPNs by activating two different K+ conductances: the voltage-insensitive IK(L) and the voltage-dependent IM. The hyperpolarizing effect of SST at resting membrane potential appears to be mainly carried by IK(L), whereas IM dominates at slightly depolarized potentials.