Multiple effects of serotonin on membrane properties of trigeminal motoneurons in vitro
Multiple effects of serotonin on membrane properties of trigeminal motoneurons in vitro
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DOI：
10.1152/jn.1997.77.6.2910
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发表时间：
1997-06-01
影响因子：
2.5
通讯作者：
Chandler, SH
中科院分区：
文献类型：
--
作者：
Hsiao, CF;Trueblood, PR;Chandler, SH
我们利用脑干切片中豚鼠三叉神经运动神经元（TMNs）的细胞内记录来确定我们之前证明的5-羟色胺（5-HT）增强下颌运动时TMN兴奋性的潜在离子机制。5-羟色胺（0.5-100 μ M）使大多数神经元去极化并增加输入电阻。此外，5-HT降低了中程超极化后的峰后振幅，降低了维持峰放电的电流阈值，增加了稳态峰频率-电流关系的最大斜率。在电压箝位下，从保持电位接近静息电位，5-HT产生向内电流，瞬时斜率电导减小，表明静息K+漏电导（I-leak）减小。在测试的大部分电压范围内，向内5-HT电流（I5-HT）的瞬时电流-电压（I-V）关系是线性的。然而，稳态I-V关系显示出在-70 mV左右开始的电位有一定程度的内向整流。瞬时1（5-HT）的平均逆转电位为-86.2 +/- 4.5 (SE) mV (n = 9)，略低于这些神经元预测的-82 mV钾平衡电位。在2mm Ba2+存在的情况下，5-HT应用不会产生输入电导的进一步降低，但确实暴露出Ba2+不敏感的残余内向电流，该电流可抵抗Cs+应用。在Ba2+存在的情况下，5-HT的瞬时I-V关系向下平移并与对照平行，表明Ba2+和5-HT阻断了相同的静息i泄漏。总向内I5-HT中残留的Ba2+和Cs+不敏感成分与电压无关，当细胞外Na+被胆碱取代时被阻断，这表明该残留电流的主要载流子是Na+。5-HT增强了超极化激活的阳离子电流I-h。在Ba2+存在的情况下，1（5-HT）的时间过程与I-h相似，并表现出类似的电压依赖性，这种依赖性被细胞外Cs+ (1-3 mM)阻断。5-HT对膜电位、输入电阻和I-h的影响部分被5-HT2激动剂模拟，并被5-HT2拮抗剂抑制。结果表明，5-羟色胺通过调节多种本征膜电导增强TMN膜的兴奋性。这提供了一种机制来微调这些神经元的输入-输出放电特性，从而使它们在响应颌骨各种运动期间随时间变化的突触输入时具有更大的输出灵活性。
Intracellular recordings from guinea pig trigeminal motoneurons (TMNs) in brain stem slices were used to determine the underlying ionic mechanisms responsible for our previously demonstrated enhancement of TMN excitability during jaw movements by serotonin (5-HT). 5-HT (0.5-100 mu M) depolarized motoneurons and increased input resistance in the majority of neurons tested. Additionally, 5-HT reduced the amplitude of the postspike medium-duration afterhyperpolarization, decreased the current threshold for maintained spike discharge, and increased the maximum slope of the steady-state spike frequency-current relationship. Under voltage clamp, from holding potentials close to resting potential, 5-HT produced an inward current and a decrease in instantaneous slope conductance, suggesting a reduction In a resting K+ leak conductance (I-leak). The instantaneous current-voltage(I-V) relationship for the inward 5-HT current (I5-HT) was linear throughout most of the voltage range tested. However, the steady-state I-V relationship showed some degree of inward rectification at potentials starting around -70 mV. The mean reversal potential for the instantaneous 1(5-HT) was -86.2 +/- 4.5 (SE) mV (n = 9), a value slightly negative to the predicted potassium equilibrium potential of -82 mV in these neurons. In the presence of 2 mM Ba2+, 5-HT application did nor produce a further reduction in input conductance, but did expose a Ba2+-insensitive residual inward current that was resistant to Cs+ application. The instantaneous I-V relationship during 5-HT application in the presence of Ba2+ was shifted downward and parallel to control, suggesting that Ba2+ and 5-HT block the same resting I-leak. The residual Ba2+- and Cs+-insensitive component of the total inward I5-HT was voltage independent and was blocked when the extracellular Na+ was replaced by choline, suggesting that the predominant charge carrier for this residual current is Na+. 5-HT enhanced a hyperpolarization-activated cationic current, I-h. In the presence of Ba2+, the time course of 1(5-HT) resembled that of I-h and showed a similar voltage dependence that was blocked by extracellular Cs+ (1-3 mM). The effects of 5-HT on membrane potential, input resistance, and I-h were partially mimicked by 5-HT2 agonists and suppressed by 5-HT2 antagonists. It is concluded that 5-HT enhances TMN membrane excitability through modulation of multiple intrinsic membrane conductances. This provides for a mechanism(s) to fine tune the input-output discharge properties of these neurons, thus providing them with greater flexibility in output in response to time-varying synaptic inputs during various movements of the jaw.