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.