Phorbol ester uncouples adenosine inhibition of presynaptic Ca2+ transients at hippocampal synapses

✍ Scribed by Gabriella Stocca; David M. Lovinger

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 276 KB
• Volume: 13
• Category: Article
• ISSN: 1050-9631
• DOI: 10.1002/hipo.10088

✦ Synopsis

Abstract

Synaptic transmission involves Ca^2+^ influx at presynaptic terminals. Adenosine receptors inhibit transmission, and this effect can be abolished by activation of PKC with phorbol esters. Whether protein kinase C (PKC) acts via alterations in Ca^2+^ entry at the presynaptic terminal is unknown. In the present study, we recorded the presynaptic Ca^2+^ transients (preCaΔ) in hippocampal stratum radiatum, using fluorescence photometry. The calcium dye Fura‐2 AM was used to load the Schaffer collateral/commissural tract and its terminals. Tetrodotoxin (TTX)‐sensitive Na^+^ channels and Cd^2+^‐sensitive, high‐voltage activated Ca^2+^ channels (HVACCs) were required to elicit the preCaΔ. Application of the phorbol ester phorbol‐12,13‐dibutyrate (PDBu) abolished the adenosine inhibition of both preCaΔ and the field excitatory postsynaptic potentials (fEPSPs). PDBu consistently potentiated fEPSPs, and also increased preCaΔ in a large majority of the slices examined. Regardless of whether potentiation was observed, PDBu always prevented adenosine inhibition of preCaΔ. In contrast, the inactive phorbol ester, 4α‐phorbol, did not alter adenosine inhibition of preCaΔ, indicating that PKC activation is necessary for the occurrence of the observed effects. Our findings suggest that PKC activation abolishes adenosine's inhibitory effect on synaptic activity involving presynaptic Ca^2+^ entry. Hippocampus 2003;13:355–360. © 2003 Wiley‐Liss, Inc.