Calcium-dependent isoforms of protein kinase C mediate posttetanic potentiation at the calyx of Held

Neuron. 2011 Jun 9;70(5):1005-19. doi: 10.1016/j.neuron.2011.04.019.

Abstract

High-frequency stimulation leads to a transient increase in the amplitude of evoked synaptic transmission that is known as posttetanic potentiation (PTP). Here we examine the roles of the calcium-dependent protein kinase C isoforms PKCα and PKCβ in PTP at the calyx of Held synapse. In PKCα/β double knockouts, 80% of PTP is eliminated, whereas basal synaptic properties are unaffected. PKCα and PKCβ produce PTP by increasing the size of the readily releasable pool of vesicles evoked by high-frequency stimulation and by increasing the fraction of this pool released by the first stimulus. PKCα and PKCβ do not facilitate presynaptic calcium currents. The small PTP remaining in double knockouts is mediated partly by an increase in miniature excitatory postsynaptic current amplitude and partly by a mechanism involving myosin light chain kinase. These experiments establish that PKCα and PKCβ are crucial for PTP and suggest that long-lasting presynaptic calcium increases produced by tetanic stimulation may activate these isoforms to produce PTP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azepines / pharmacology
  • Biophysics
  • Calcium / metabolism*
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / genetics
  • Excitatory Postsynaptic Potentials / physiology*
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Patch-Clamp Techniques
  • Phorbol Esters / pharmacology
  • Presynaptic Terminals / physiology
  • Protein Kinase C / deficiency
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Protein Kinase C-alpha / deficiency
  • Protein Kinase C-alpha / metabolism*
  • Synapses / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics
  • Tectum Mesencephali / cytology*
  • Teprotide / pharmacology
  • Vesicular Glutamate Transport Protein 1 / metabolism

Substances

  • Azepines
  • Phorbol Esters
  • Slc17a7 protein, mouse
  • Vesicular Glutamate Transport Protein 1
  • ML 9
  • Teprotide
  • Protein Kinase C
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Calcium