Walsh J P, Byrne J H
J Neurophysiol. 1985 Feb;53(2):590-602. doi: 10.1152/jn.1985.53.2.590.
Micropressure ejection of serotonin (5-hydroxytryptamine, 5-HT) produced excitatory responses in the L14 ink motor neurons of Aplysia that depended on the site of application. Ejection of 5-HT onto the cell body produced a slow response that showed variability in voltage sensitivity between preparations. In contrast, ejection of 5-HT onto the neuropil underneath the cell body produced a response whose amplitude was consistently a linear function of the holding potential, reversing near the predicted potassium equilibrium potential. Subsequent analyses focused on this second response. The neuropil response induced by 5-HT had a linear current-voltage relationship (reversing at ca. -80 mV), was associated with a decrease in input conductance, and was sensitive to changes in the concentration of extracellular K+. Serotonin application in artificial seawater (ASW) containing 30 mM K+ produced a response that reversed close to the altered Nernst potential for K+. The 5-HT response did not appear to be due to secondary activation of interneurons or to depend primarily on extracellular Ca2+, since ejection of 5-HT onto cells bathed in ASW containing 30 mM Co2+ produced responses comparable to, although somewhat attenuated from, those observed in ASW. Serotonin responses similar to those produced in ASW were obtained after perfusing the ganglion with ASW containing Co2+, 4-aminopyridine (4-AP), and tetraethylammonium (TEA). This suggests that the 5-HT-sensitive current is separate from the Ca2+-activated, fast, and delayed rectifying K+ currents. The 5-HT response appeared to be mediated by changes in levels of cAMP. Bath application of the phosphodiesterase inhibitors IBMX (3-isobutyl-1-methylxanthine) or Ro 20-1724, or the adenylate cyclase activator forskolin mimicked the 5-HT response by producing a slow inward current associated with a decrease in membrane conductance. Alteration of cellular cAMP metabolism modulated the response to 5-HT. Exposure of the ganglion to low concentrations of either Ro 20-1724 or forskolin potentiated the 5-HT response. Higher concentrations of these agents largely blocked the response to subsequent 5-HT applications. Bath application of the 8-bromo derivative of either cAMP or cGMP produced a slow inward current associated with a decrease in membrane conductance in cells voltage clamped at the resting potential. Responses to 5-HT were blocked, however, after exposure to 8-bromo-cAMP, but not to 8-bromo-cGMP. These results suggest that 5-HT produces a voltage-independent decrease in a steady-state potassium conductance that may be mediated by cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
微量注射血清素（5-羟色胺，5-HT）可在海兔的L14墨水运动神经元中产生兴奋性反应，该反应取决于注射部位。将5-HT注射到细胞体上会产生缓慢的反应，不同标本间电压敏感性存在差异。相比之下，将5-HT注射到细胞体下方的神经纤维网上会产生一种反应，其幅度始终是静息电位的线性函数，在接近预测的钾平衡电位时反转。后续分析聚焦于这第二种反应。5-HT诱导的神经纤维网反应具有线性电流-电压关系（在约-80 mV处反转），与输入电导降低相关，且对细胞外K+浓度变化敏感。在含有30 mM K+的人工海水中施加血清素会产生一种反应，该反应在接近改变后的K+能斯特电位处反转。5-HT反应似乎并非由于中间神经元的二次激活，也不主要依赖细胞外Ca2+，因为将5-HT注射到浸泡在含有30 mM Co2+的人工海水中的细胞上会产生与在人工海水中观察到的反应相当的反应，尽管有所减弱。在用含有Co2+、4-氨基吡啶（4-AP）和四乙铵（TEA）的人工海水灌注神经节后，获得了与在人工海水中产生的类似的血清素反应。这表明5-HT敏感电流与Ca2+激活的、快速和延迟整流的K+电流不同。5-HT反应似乎是由cAMP水平的变化介导的。浴槽中施加磷酸二酯酶抑制剂IBMX（3-异丁基-1-甲基黄嘌呤）或Ro 20-1724，或腺苷酸环化酶激活剂福斯可林，通过产生与膜电导降低相关的缓慢内向电流来模拟5-HT反应。细胞cAMP代谢的改变调节了对5-HT的反应。将神经节暴露于低浓度的Ro 20-1724或福斯可林中可增强5-HT反应。这些药物的较高浓度在很大程度上阻断了对后续5-HT施加的反应。在静息电位钳制的细胞中，浴槽中施加cAMP或cGMP的8-溴衍生物会产生与膜电导降低相关的缓慢内向电流。然而，在暴露于8-溴-cAMP后，对5-HT的反应被阻断，但暴露于8-溴-cGMP后未被阻断。这些结果表明，5-HT会使稳态钾电导产生电压非依赖性降低，这可能由cAMP介导。（摘要截短于400字）
