Tonically active protein kinase A regulates neurotransmitter release at the squid giant synapse

Sabine Hilfiker, Andrew J. Czernik, Paul Greengard, George J. Augustine

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


1. Electrophysiological and microinjection methods were used to examine the role of cyclic AMP-dependent protein kinase A (PKA) in regulating transmitter release at the squid giant synapse. 2. Excitatory postsynaptic potentials (EPSPs) evoked by presynaptic action potentials were not affected by presynaptic injection of an exogenous active catalytic subunit of mammalian PKA. 3. In contrast, presynaptic injection of PKI-amide, a peptide that inhibits PKA with high potency and specificity, led to a reversible inhibition of EPSPs. 4. Injection of several other peptides that serve as substrates for PKA also reversibly inhibited neurotransmitter release. The ability of these peptides to inhibit release was correlated with their ability to serve as PKA substrates, suggesting that these peptides act by competing with endogenous substrates for phosphorylation by active endogenous PKA. 5. We suggest that the phosphorylation of PKA substrates is maintained at a relatively high state under basal conditions and that this tonic activity of PKA is to a large degree required for evoked neurotransmitter release at the squid giant presynaptic terminal.

Original languageEnglish (US)
Pages (from-to)141-146
Number of pages6
JournalJournal of Physiology
Issue number1
StatePublished - Feb 15 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology


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