Department of Anesthesiology

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Balance of calcineurin Aα and CDK5 activities sets release probability at nerve terminals.

TitleBalance of calcineurin Aα and CDK5 activities sets release probability at nerve terminals.
Publication TypeJournal Article
Year of Publication2013
AuthorsKim SHyun, Ryan TA
JournalJ Neurosci
Volume33
Issue21
Pagination8937-50
Date Published2013 May 22
ISSN1529-2401
KeywordsAction Potentials, Animals, Animals, Newborn, Calcineurin, Calcium, Calcium Channel Blockers, Cells, Cultured, Cyclin-Dependent Kinase 5, Exocytosis, Hippocampus, Luminescent Proteins, Nerve Endings, Neurons, omega-Agatoxin IVA, Photic Stimulation, Probability, Rats, Rats, Sprague-Dawley, RNA, Small Interfering, Transfection, Vesicle-Associated Membrane Protein 2
Abstract

The control of neurotransmitter release at nerve terminals is of profound importance for neurological function and provides a powerful control system in neural networks. We show that the balance of enzymatic activities of the α isoform of the phosphatase calcineurin (CNAα) and the kinase cyclin-dependent kinase 5 (CDK5) has a dramatic influence over single action potential (AP)-driven exocytosis at nerve terminals. Acute or chronic loss of these enzymatic activities results in a sevenfold impact on single AP-driven exocytosis. We demonstrate that this control is mediated almost entirely through Cav2.2 (N-type) voltage-gated calcium channels as blocking these channels with a peptide toxin eliminates modulation by these enzymes. We found that a fraction of nerve terminals are kept in a presynaptically silent state with no measurable Ca(2+) influx driven by single AP stimuli attributable to the balance of CNAα and CDK5 activities because blockade of either CNAα or CDK5 activity changes the proportion of presynaptically silent nerve terminals. Thus, CNAα and CDK5 enzymatic activities are key determinants of release probability.

DOI10.1523/JNEUROSCI.4288-12.2013
Alternate JournalJ. Neurosci.
PubMed ID23699505
PubMed Central IDPMC3808255
Grant ListMH085783 / MH / NIMH NIH HHS / United States
NS036942 / NS / NINDS NIH HHS / United States
R01 MH085783 / MH / NIMH NIH HHS / United States
R01 NS036942 / NS / NINDS NIH HHS / United States