Activation of CRH receptor type 1 expressed on glutamatergic neurons increases excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion channels.
Activation of CRH receptor type 1 expressed on glutamatergic neurons increases excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion channels.
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DOI：
10.3389/fncel.2013.00091
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发表时间：
2013
影响因子：
5.3
通讯作者：
Rammes G
中科院分区：
文献类型：
--
作者：
Kratzer S;Mattusch C;Metzger MW;Dedic N;Noll-Hussong M;Kafitz KW;Eder M;Deussing JM;Holsboer F;Kochs E;Rammes G
促肾上腺皮质激素释放激素（CRH）在许多应激相关精神障碍（如焦虑症和抑郁症）患者中起重要作用。CRH已被证明可以增加海马神经元的兴奋性，但其潜在机制尚不清楚。在急性海马脑片上观察了CRH对神经元兴奋性的影响。群体棘波（PS）和场兴奋性突触后电位（fEPSP）诱发的刺激Schaffer侧支，并同时记录从体和树突区的CA 1锥体神经元。发现CRH增加PS振幅（平均值±平均值的标准误差;对照的231.8 ± 31.2%; n = 10），而不影响fEPSP（104.3 ± 4.2%; n = 10）或长时程增强（LTP）。然而，当通过刺激CA 3锥体神经元产生的动作电位（AP）兴奋Schaffer侧支时，CRH增加了CA 1区的fEPSP振幅（119.8 ± 3.6%; n = 8）和LTP的幅度。转基因小鼠脑片实验表明，PS振幅的影响是由CRH受体1（CRHR 1）介导的，CRHR 1表达在多巴胺能神经元上。CRH对PS的作用依赖于磷酸酶-2B、L-和T-型钙通道和电压门控钾通道，但不依赖于细胞内Ca ~（2+）升高。在膜片钳实验中，CRH增加AP的频率和衰减时间，并降低通过A型和延迟整流钾通道的电流。这些结果表明，CRH不影响突触传递本身，但调制电压门控离子电流重要的AP的产生，因此通过这条路线提高整体神经元的活动。
Corticotropin-releasing hormone (CRH) plays an important role in a substantial number of patients with stress-related mental disorders, such as anxiety disorders and depression. CRH has been shown to increase neuronal excitability in the hippocampus, but the underlying mechanisms are poorly understood. The effects of CRH on neuronal excitability were investigated in acute hippocampal brain slices. Population spikes (PS) and field excitatory postsynaptic potentials (fEPSP) were evoked by stimulating Schaffer-collaterals and recorded simultaneously from the somatic and dendritic region of CA1 pyramidal neurons. CRH was found to increase PS amplitudes (mean ± Standard error of the mean; 231.8 ± 31.2% of control; n = 10) while neither affecting fEPSPs (104.3 ± 4.2%; n = 10) nor long-term potentiation (LTP). However, when Schaffer-collaterals were excited via action potentials (APs) generated by stimulation of CA3 pyramidal neurons, CRH increased fEPSP amplitudes (119.8 ± 3.6%; n = 8) and the magnitude of LTP in the CA1 region. Experiments in slices from transgenic mice revealed that the effect on PS amplitude is mediated exclusively by CRH receptor 1 (CRHR1) expressed on glutamatergic neurons. The effects of CRH on PS were dependent on phosphatase-2B, L- and T-type calcium channels and voltage-gated potassium channels but independent on intracellular Ca2+-elevation. In patch-clamp experiments, CRH increased the frequency and decay times of APs and decreased currents through A-type and delayed-rectifier potassium channels. These results suggest that CRH does not affect synaptic transmission per se, but modulates voltage-gated ion currents important for the generation of APs and hence elevates by this route overall neuronal activity.
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影响因子：
5.3
作者：
Chen, YC;Bender, RA;Baram, TZ
通讯作者：
Baram, TZ
影响因子：
4.1
作者：
Jose Bonfiglio, Juan;Inda, Carolina;Silberstein, Susana
通讯作者：
Silberstein, Susana
影响因子：
2.3
作者：
LEE, EHY;LEE, CP;LIN, WR
通讯作者：
LIN, WR
影响因子：
56.9
作者：
ALDENHOFF, JB;GRUOL, DL;SIGGINS, GR
通讯作者：
SIGGINS, GR
DOI：
10.1111/j.1749-6632.1999.tb11293.x
发表时间：
1999-01-01
期刊：
MOLECULAR AND FUNCTIONAL DIVERSITY OF ION CHANNELS AND RECEPTORS
影响因子：
--
作者：
Coetzee, WA;Amarillo, Y;Rudy, B
通讯作者：
Rudy, B