Hsiao C F, Trueblood P R, Levine M S, Chandler S H
Department of Physiological Science and the Mental Retardation Center, University of California at Los Angeles, 90095, USA.
J Neurophysiol. 1997 Jun;77(6):2910-24. doi: 10.1152/jn.1997.77.6.2910.
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 microM) 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 (I(5-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 I(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 not 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 I(5-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 I(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.
利用豚鼠脑干切片中三叉神经运动神经元（TMNs）的细胞内记录，来确定导致我们之前所证明的血清素（5-HT）在颌部运动期间增强TMN兴奋性的潜在离子机制。5-HT（0.5 - 100微摩尔）使大多数被测试的运动神经元去极化并增加输入电阻。此外，5-HT降低了峰后中等时程超极化的幅度，降低了维持动作电位发放的电流阈值，并增加了稳态动作电位频率-电流关系的最大斜率。在电压钳制下，从接近静息电位的钳制电位开始，5-HT产生内向电流并使瞬时斜率电导降低，提示静息钾离子泄漏电导（I(leak)）降低。在测试的大部分电压范围内，内向5-HT电流（I(5-HT)）的瞬时电流-电压（I-V）关系呈线性。然而，稳态I-V关系在约-70 mV左右的电位开始显示出一定程度的内向整流。瞬时I(5-HT)的平均反转电位为-86.2±4.5（SE）mV（n = 9），该值略负于这些神经元中预测的钾离子平衡电位-82 mV。在存在2 mM Ba2+的情况下，施加5-HT不会进一步降低输入电导，但会暴露出对Ba2+不敏感的残余内向电流，该电流对施加Cs+有抗性。在存在Ba2+的情况下施加5-HT期间的瞬时I-V关系向下移位并与对照平行，提示Ba2+和5-HT阻断相同的静息I(leak)。总内向I(5-HT)中对Ba2+和Cs+不敏感的残余成分与电压无关，当细胞外Na+被胆碱取代时被阻断，提示该残余电流的主要电荷载体是Na+。5-HT增强了超极化激活的阳离子电流I(h)。在存在Ba2+的情况下，I(5-HT)的时间进程类似于I(h)，并显示出类似的电压依赖性，被细胞外Cs+（1 - 3 mM）阻断。5-HT对膜电位、输入电阻和I(h)的作用部分被5-HT2激动剂模拟，被5-HT2拮抗剂抑制。结论是5-HT通过调节多种内在膜电导来增强TMN膜兴奋性。这为微调这些神经元的输入-输出发放特性提供了一种机制，从而使它们在颌部各种运动期间对随时间变化的突触输入做出反应时，在输出方面具有更大的灵活性。
