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Co‐activation of PKA and PKC in cerebrocortical nerve terminals synergistically facilitates glutamate release
Author(s) -
Millán Carmelo,
Torres Magdalena,
SánchezPrieto José
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02065.x
Subject(s) - protein kinase c , protein kinase a , tetrodotoxin , microbiology and biotechnology , glutamate receptor , forskolin , glutamatergic , activator (genetics) , staurosporine , chemistry , kinase , biology , biophysics , biochemistry , receptor
Protein kinase A and protein kinase C are involved in processes that enhance glutamate release at glutamatergic nerve terminals. However, it is not known whether these two kinases co‐exist within the same nerve terminal, nor is it clear what impact their simultaneous activation may have on neurotransmitter release. In cerebrocortical nerve terminals, co‐application of forskolin, which increases cAMP levels and activates protein kinase A, and 4β‐phorbol dibutyrate, a direct activator of protein kinase C, synergistically enhanced the spontaneous release of glutamate. This enhancement exhibited both tetrodotoxin‐sensitive and tetrodotoxin‐resistant components. Interestingly, the tetrodotoxin‐resistant component of release was not observed when cyclic AMP‐dependent protein kinase (PKA) and calcium‐ and phospholipid‐dependent protein kinase (PKC) were activated separately, but developed slowly after the co‐activation of the two kinases, accounting for 50% of the facilitated release. This release component was dependent on voltage‐dependent Ca 2+ channels that opened spontaneously after PKA and PKC activation and occurred in the absence of Na + channel firing. These data provide functional evidence for the co‐existence of PKA‐ and PKC‐signalling pathways in a subpopulation of glutamatergic nerve terminals.