Cellular Physiology and Biochemistry | |
Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons | |
Mengwen Qi1  | |
关键词: Transient receptor potential vanilloid 4; Glycine receptor; Phosphorylation; Protein kinase C; Calcium/calmodulin-dependent protein kinase II; Glycine receptor subunit expression; | |
DOI : 10.1159/000487350 | |
学科分类:分子生物学,细胞生物学和基因 | |
来源: S Karger AG | |
【 摘 要 】
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.
【 授权许可】
CC BY-NC-ND
【 预 览 】
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