Recordings From Single Neocortical Nerve Terminals Reveal a Nonselective Cation Channel Activated by Decreases in Extracellular Calcium

Neuron. 2004 Jan 22;41(2):243-56. doi: 10.1016/s0896-6273(03)00837-7.

Abstract

Synaptic activity causes reductions in cleft [Ca(2+)] that may impact subsequent synaptic efficacy. Using modified patch-clamp techniques to record from single neocortical nerve terminals, we report that physiologically relevant reductions of extracellular [Ca(2+)] ([Ca(2+)](o)) activate voltage-dependent outward currents. These outward currents are carried by a novel nonselective cation (NSC) channel that is indirectly inhibited by various extracellular agents (rank order potency, Gd(3+) > spermidine > Ca(2+) > Mg(2+), typical for [Ca(2+)](o) receptors). The identification of a Ca(2+) sensor-NSC channel pathway establishes the existence of a mechanism by which presynaptic terminals can detect and respond to reductions in cleft [Ca(2+)]. Activation of NSC channels by falls in [Ca(2+)](o) would be expected during periods of high activity in the neocortex and may modulate the excitability of the presynaptic terminal.

Publication types

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

MeSH terms

  • Calcium / metabolism*
  • Calcium / physiology
  • Calcium Signaling / physiology
  • Cations, Divalent / pharmacology
  • Extracellular Space / physiology
  • Fluorometry
  • Humans
  • Ion Channel Gating / physiology
  • Ion Channels / physiology*
  • Membrane Potentials / physiology
  • Microscopy, Electron
  • Neocortex / cytology
  • Neocortex / physiology*
  • Neurotransmitter Agents / metabolism
  • Patch-Clamp Techniques
  • Presynaptic Terminals / physiology*
  • Receptors, Calcium-Sensing / physiology
  • Synaptosomes / metabolism
  • Synaptosomes / physiology

Substances

  • Cations, Divalent
  • Ion Channels
  • Neurotransmitter Agents
  • Receptors, Calcium-Sensing
  • Calcium