Lithium Carbonate Modulation of Delayed Rectifier Potassium Channel Involves Protein Kinase C/Mitogen-activated Protein Kinase Signaling in Hippocampus of Rats
- VernacularTitle:碳酸锂通过蛋白激酶C/丝裂原活化蛋白激酶信号调节海马神经元延迟整流钾通道
- Author:
Guohui JIAO
;
Zhaowei LIU
;
Tao ZHANG
;
Zhuo YANG
- Publication Type:Journal Article
- Keywords:
hippocampus;
lithium carbonate;
delayed rectifier potassium currents;
PKC;
ERK
- From:
Progress in Biochemistry and Biophysics
2008;35(7):814-821
- CountryChina
- Language:Chinese
-
Abstract:
Lithium carbonate could be used to treat or prevent brain damage following traumatic injury and neurodegenerative diseases.It has been shown that its protective effect is related to protein kinase C (PKC) and extracellular signal-related kinase (ERK).It was demonstrated that PDBu,a PKC activator,inhibited amplitudes of delayed rectifier potassium current (It,) and produced a hyperpolarizing shift in the activation-voltage curve.The responses to PDBu were inhibited by lithium carbonate (50μmol/L).Further studies showed that when pretreated with MEK/ERK inhibitor U0126 (20 μmol/L),although PDBu significantly reduced IK,lithium did not reverse the effect of PDBu.Thus,the results suggested that PKC signaling cascades,along with MAPK (mitogen-activated protein kinase) pathway,were required in the phosphorylation of potassium channel,which was presented by regulation of potassium channel characteristic.AC-cAMP and their eross-talk with GC-cGMP pathway could also modulate the effect of lithium on PKC activation,which could be one of underlying mechanisms likely related to neuroprotective effect of lithium.
