Regulation of transmitter release by Ca(2+) and synaptotagmin: insights from a large CNS synapse

Trends Neurosci. 2011 May;34(5):237-46. doi: 10.1016/j.tins.2011.02.006. Epub 2011 Mar 24.

Abstract

Transmitter release at synapses is driven by elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) near the sites of vesicle fusion. [Ca(2+)](i) signals of profoundly different amplitude and kinetics drive the phasic release component during a presynaptic action potential, and asynchronous release at later times. Studies using direct control of [Ca(2+)](i) at a large glutamatergic terminal, the calyx of Held, have provided significant insight into how intracellular Ca(2+) regulates transmitter release over a wide concentration range. Synaptotagmin-2 (Syt2), the major isoform of the Syt1/2 Ca(2+) sensors at these synapses, triggers highly Ca(2+)-cooperative release above 1μM [Ca(2+)](i), but suppresses release at low [Ca(2+)](i). Thus, neurons utilize a highly sophisticated release apparatus to maximize the dynamic range of Ca(2+)-evoked versus spontaneous release.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / physiology*
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Computer Simulation
  • Feedback, Physiological / physiology
  • Humans
  • Models, Neurological*
  • Neurotransmitter Agents / metabolism
  • Synapses / physiology*
  • Synaptic Transmission / physiology*
  • Synaptotagmins / metabolism*

Substances

  • Neurotransmitter Agents
  • Synaptotagmins
  • Calcium