Balance of calcineurin Aα and CDK5 activities sets release probability at nerve terminals. Academic Article uri icon

Overview

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.

publication date

  • May 22, 2013

Research

keywords

  • Calcineurin
  • Cyclin-Dependent Kinase 5
  • Nerve Endings
  • Neurons
  • Probability

Identity

PubMed Central ID

  • PMC3808255

Scopus Document Identifier

  • 84877932096

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.6636-10.2011

PubMed ID

  • 23699505

Additional Document Info

volume

  • 33

issue

  • 21