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[P19]: Activation of the tyro‐3 RPTK by its ligand Gas6 and by glutamate in cortical neurons
Author(s) -
Prieto A.L,
O'Dell S.,
Weber J.,
Lai C.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.083
Subject(s) - library science , citation , ligand (biochemistry) , computer science , chemistry , receptor , biochemistry
Recently, it has been shown that H2O2, one of the most stable and long-lived ROS, are produced and released during neuromuscular activity and play important roles in modulating synaptic activity. Less is known, however, about the underlying mechanism of H2O2 on synaptic facilitation. Methods: Whole-cell patch clamp recording in one-day-old Xenopus nerve–muscle coculture were used. Results: Exclusion of calcium from culture medium or bath application of calcium channel inhibitor either cadmium, nifedipine, verapamil or -conotoxin significantly reduced H2O2 induced synaptic facilitation. Pretreatment of catalase and N-acetyl-l-cysteine effectively hampered H2O2 induced SSC frequency elevation. Preincubation of the cultures with either inhibitor of IP3 receptor XeC or ryanodine receptor TMB8 or depletion of ER Ca stores with thapsigargin failed to abolish the synaptic facilitation elicited by H2O2. Bath application of mitochondrial Na–Ca exchanger inhibitor FCCP or CGP37157 partialy obstructed the increase of SSC frequency in response to H2O2. Treating cells with protein kinase C inhibitors either H-9 or GF 109203X effectively occluded the increase of SSC frequency elicited by H2O2. Furthermore, application of either phosphatidyl inositol 3 kinase (PI3K) inhibitor wortmannin or phospholipase C (PLC ) inhibitor U73122, also abolished H2O2-induced facilitation of synaptic transmission. Discussion: Overall, results from our current study indicate that both calcium influx through Land N-type Ca channel and efflux from mitochondrial are responsible for H2O2-induced SSC frequency facilitation. This is done via PLC /PI3K, PKC activation and Na–Ca exchanger blockade.