Activation of the epsilon isoform of protein kinase C in the mammalian nerve terminal

AUTOR(ES)

Saitoh, Naoto

FONTE

The National Academy of Sciences

RESUMO

Activation of protein kinase C (PKC) by phorbol ester facilitates hormonal secretion and transmitter release, and phorbol ester-induced synaptic potentiation (PESP) is a model for presynaptic facilitation. A variety of PKC isoforms are expressed in the central nervous system, but the isoform involved in the PESP has not been identified. To address this question, we have applied immunocytochemical and electrophysiological techniques to the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) of rat auditory brainstem. Western blot analysis indicated that both the Ca2+-dependent “conventional” PKC and Ca2+-independent “novel” PKC isoforms are expressed in the MNTB. Denervation of afferent fibers followed by organotypic culture, however, selectively decreased “novel” ɛPKC isoform expressed in this region. The afferent calyx terminal was clearly labeled with the ɛPKC immunofluorescence. On stimulation with phorbol ester, presynaptic ɛPKC underwent autophosphorylation and unidirectional translocation toward the synaptic side. Chelating presynaptic Ca2+, by using membrane permeable EGTA analogue or high concentration of EGTA directly loaded into calyceal terminals, had only a minor attenuating effect on the PESP. We conclude that the Ca2+-independent ɛPKC isoform mediates the PESP at this mammalian central nervous system synapse.

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