Feedback mechanism in depolarization-induced sustained activation of extracellular signal-regulated kinase in the hippocampus.
Phosphorylation plays important roles in several processes including synaptic plasticity and memory. The critical role of extracellular signal-regulated kinase (ERK) in these processes is well established. ERK is activated in a sustained manner by different stimuli. However, the mechanisms of sustained ERK activation are not completely understood. Here we show that KCl depolarization-induced sustained ERK activation in the hippocampal slices is critically dependent on protein synthesis and transcription. In addition, the sustained ERK activation requires receptor tyrosine kinase(s) activity. In support of a role for a growth factor in sustained ERK activation, KCl depolarization enhances the level of brain-derived neurotrophic factor (BDNF). Furthermore, BDNF antibody blocks KCl-induced sustained ERK activation. These results suggest a positive feed-back loop in which depolarization-induced BDNF maintains ERK activation in the sustained phase.
National Brain Research Centre, Manesar, Haryana-122051 India.
Chinmoyee
C
Maharana
Kaushik P
KP
Sharma
Shiv K
SK
Sharma
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D025461:Feedback, Physiological; D006624:Hippocampus / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D011189:Potassium Chloride / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic
D019208:Brain-Derived Neurotrophic Factor; D011189:Potassium Chloride; D048049:Extracellular Signal-Regulated MAP Kinases