The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse

Neuron. 2005 May 19;46(4):633-45. doi: 10.1016/j.neuron.2005.03.024.

Abstract

Repetitive nerve firings cause short-term depression (STD) of release at many synapses. Its underlying mechanism is largely attributed to depletion of a readily releasable vesicle pool (RRP) and a decreased probability of releasing a readily releasable vesicle during an action potential. Which of these two mechanisms is dominant and the mechanism that decreases the release probability remain debated. Here, we report that a decreased release probability is caused by a calcium-induced inhibition of presynaptic calcium channels, particularly P/Q-type channels at the calyx of Held in rat brainstem. This mechanism was the dominant cause of STD in a wide range of stimulation conditions, such as during 2 to 20 action potential-equivalent stimuli (AP-e) at 0.2-30 Hz and after 2 to 20 AP-e at 0.2-100 Hz. Only during > or = 100 Hz AP-e was depletion the dominant mechanism.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Action Potentials / radiation effects
  • Animals
  • Animals, Newborn
  • Barium / pharmacology
  • Brain Stem / cytology
  • CREB-Binding Protein
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Calcium Channels / radiation effects
  • Chelating Agents / pharmacology
  • Dose-Response Relationship, Radiation
  • Egtazic Acid / analogs & derivatives*
  • Egtazic Acid / pharmacology
  • Electric Capacitance
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Models, Biological
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neural Inhibition / radiation effects
  • Nuclear Proteins / pharmacology
  • Patch-Clamp Techniques / methods
  • Peptides / pharmacology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Rats
  • Rats, Wistar
  • Synapses / metabolism*
  • Time Factors
  • Trans-Activators / pharmacology

Substances

  • Calcium Channels
  • Chelating Agents
  • Enzyme Inhibitors
  • Imidazoles
  • Nuclear Proteins
  • Peptides
  • Trans-Activators
  • MLCK peptide
  • Barium
  • calmidazolium
  • Egtazic Acid
  • CREB-Binding Protein
  • Crebbp protein, rat
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium