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首页> 外文期刊>Cellular Physiology and Biochemistry >Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons
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Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons

机译：小鼠海马锥体神经元中甘氨酸激活电流的瞬时受体潜在香草酸4激活诱导的增加。

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Background/Aims Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods Whole-cell patch clamp recording was employed to record glycine-activated current (IGly) and Western blot was conducted to assess GlyRs subunits protein expression. Results Application of TRPV4 agonist (GSK1016790A or 5,6-EET) increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047) and GlyR (strychnine), indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC) (BIM II or D-sphingosine) or calcium/calmodulin-dependent protein kinase II (CaMKII) (KN-62 or KN-93) antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv.) injected with GSK1016790A for 5 d. Conclusion Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.
机译：背景/目的甘氨酸通过激活甘氨酸受体（GlyRs）并作为N-甲基-d-天冬氨酸型谷氨酸受体的共激动剂，在调节海马抑制/兴奋性神经传递中起重要作用。据报道，瞬时受体电位香草酸4（TRPV4）的激活可抑制海马A型γ-氨基丁酸受体（配体门控氯离子通道）。 GlyRs也是配体门控的氯离子通道，本文旨在探讨TRPV4的激活是否可以调节GlyRs。方法采用全细胞膜片钳记录法记录甘氨酸激活电流（IGly），并进行Western blot检测GlyRs亚基的蛋白表达。结果TRPV4激动剂（GSK1016790A或5,6-EET）在小鼠海马CA1锥体神经元中的IGly升高。该作用被TRPV4（RN-1734或HC-067047）和GlyR（司替宁）的特异性拮抗剂所阻断，表明TRPV4的激活增加了小鼠海马锥体神经元中对士的宁敏感的GlyR功能。 GSK1016790A诱导的IGly升高被蛋白激酶C（PKC）（BIM II或D-鞘氨醇）或钙/钙调蛋白依赖性蛋白激酶II（CaMKII）（KN-62或KN-93）拮抗剂显着减弱，但不受其影响蛋白激酶A或蛋白酪氨酸激酶拮抗剂。最后，用GSK1016790A处理30分钟或1小时后，GlyRα1α2，α3和β亚基的海马蛋白水平没有改变，但脑室内注射（icv。）的小鼠中GlyRα2，α3和β亚基的蛋白水平却升高了。 GSK1016790A 5天。结论TRPV4的激活增加了GlyR的功能和表达，PKC和CaMKII信号通路参与了TRPV4激活引起的IGly的增加。这项研究表明，GlyRs可能是TRPV4诱导的海马抑制性神经传递调节的有效靶标。

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