Serotonergic modulation of the hyperpolarizing spike afterpotential in rat jaw-closing motoneurons by PKA and PKC.
Serotonergic modulation of the hyperpolarizing spike afterpotential in rat jaw-closing motoneurons by PKA and PKC.
复制标题
PKA 和 PKC 对大鼠闭颌运动神经元超极化尖峰后电位的血清素调节。
DOI：
10.1152/jn.1999.82.2.626
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发表时间：
1999
影响因子：
2.5
通讯作者：
T. Morimoto
中科院分区：
文献类型：
--
作者：
T. Inoue;S. Itoh;M. Kobayashi;Y. Kang;R. Matsuo;S. Wakisaka;T. Morimoto
本研究采用大鼠下颌闭合运动神经元（JCMNs）脑片细胞内记录方法，观察5-羟色胺（5-HT）对大鼠下颌闭合运动神经元（JCMNs）锋电位后中时程后超极化（mAHP）的影响，并探讨蛋白激酶在这种影响中的作用。应用50 μ M 5-HT引起膜去极化和增加输入电阻在大多数细胞中不影响mAHP，而不仅膜去极化和输入电阻的增加，而且mAHP幅度的抑制由较高剂量的5-HT（100或200 μ M）诱导。另一方面，当通过将[Ca（2+）]（o）从2 mM提高到6 mM来增加mAHP振幅时，5-HT诱导的mAHP振幅的衰减增强，并且甚至50 μ M的5-HT也降低mAHP振幅。这种5-HT诱导的mAHP抑制可以通过应用膜渗透性cAMP类似物8-溴-cAMP来模拟，通过cAMP特异性磷酸二酯酶抑制剂Ro 20-1724来增强，并通过蛋白激酶A（PKA）抑制剂H89来拮抗。在[Ca（2+）]（o）升高的情况下，50 μ M 5-HT诱导的mAHP衰减的增强被蛋白激酶C（PKC）抑制剂白屈菜红碱阻断，表明PKC参与了这种增强。另一方面，由PKC激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯诱导的mAHP的衰减几乎完全被H89阻断，这表明PKC对mAHP的作用需要PKA激活。5-HT（1A）拮抗剂NAN-190或5-HT（4）拮抗剂SB 203186均不能阻断5-HT诱导的mAHP的衰减。我们得出结论，5-HT通过cAMP依赖性PKA激活诱导mAHP振幅的剂量依赖性衰减，并且PKC依赖性PKA激活也可能参与5-HT诱导的[Ca（2+）]（o）升高下mAHP衰减的增强。因为只有当mAHP幅度被5-HT降低时，放电频率和注入电流之间的线性关系的斜率才增加，所以建议JCMNs中传入突触输入和放电输出之间的关系根据JCMNs的钙能效应和其效应的钙依赖性调制而变化。
Intracellular recordings were obtained from rat jaw-closing motoneurons (JCMNs) in slice preparations to investigate the effects of serotonin (5-HT) on the postspike medium-duration afterhyperpolarization (mAHP) and an involvement of protein kinases in the effects. Application of 50 microM 5-HT caused membrane depolarization and increased input resistance in the most cells without affecting the mAHP, whereas not only membrane depolarization and an increase in input resistance, but also the suppression of the mAHP amplitude was induced by higher dose of 5-HT (100 or 200 microM). On the other hand, when the mAHP amplitude was increased by raising [Ca(2+)](o) from 2 to 6 mM, 5-HT-induced attenuation of the mAHP amplitude was enhanced, and even 50 microM 5-HT reduced the mAHP amplitude. This 5-HT-induced suppression of the mAHP could be mimicked by application of membrane-permeable cAMP analogue 8-Bromo-cAMP, potentiated by the cAMP-specific phosphodiesterase inhibitor Ro 20-1724 and antagonized by protein kinase A (PKA) inhibitor H89. The enhancement of the mAHP attenuation induced by 50 microM 5-HT under raised [Ca(2+)](o) was blocked by a protein kinase C (PKC) inhibitor chelerythrine, suggesting an involvement of PKC in this enhancement. On the other hand, the attenuation of the mAHP induced by PKC activator phorbol 12-myristate 13-acetate was blocked almost completely by H89, suggesting that the PKC action on the mAHP requires PKA activation. Neither 5-HT(1A) antagonist NAN-190 or 5-HT(4) antagonist SB 203186 blocked 5-HT-induced attenuation of the mAHP. We conclude that 5-HT induces dose-dependent attenuation of the mAHP amplitude through cAMP-dependent activation of PKA and that PKC-dependent PKA activation is also likely to be involved in the enhancement of 5-HT-induced attenuation of the mAHP under raised [Ca(2+)](o). Because the slope of the linear relationship between firing frequency and injected current was increased only when the mAHP amplitude was decreased by 5-HT, it is suggested that the relation between incoming synaptic inputs and firing output in JCMNs varies according to serotonergic effects on JCMNs and calcium-dependent modulation of its effects.
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影响因子：
2.5
作者：
Hsiao, CF;Trueblood, PR;Chandler, SH
通讯作者：
Chandler, SH
成人海马神经元 5-HT4 受体介导反应的拮抗剂。
DOI：
--
发表时间：
1994
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Torres,GE;Holt,IL;Andrade,R
通讯作者：
Andrade,R
环 AMP 和蛋白激酶 A 介导 5-羟色胺 4 型受体对成人海马神经元钙激活钾电流的调节。
DOI：
--
发表时间：
1995
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Torres,GE;Chaput,Y;Andrade,R
通讯作者：
Andrade,R
影响因子：
2.5
作者：
Bayliss, DA;Li, YW;Talley, EM
通讯作者：
Talley, EM
5-羟色胺 4 受体通过抑制钙诱导的钙释放来减少海马的后超极化。
DOI：
--
发表时间：
1996
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Torres,GE;Arfken,CL;Andrade,R
通讯作者：
Andrade,R