Different localizations and functions of L-type and N-type calcium channels during development of hippocampal neurons

Dev Biol. 2000 Nov 15;227(2):581-94. doi: 10.1006/dbio.2000.9872.

Abstract

Using immunocytochemical assays and patch-clamp and calcium-imaging recordings, we demonstrate that L-type and N-type calcium channels have distinct patterns of expression and distribution and play different functional roles during hippocampal neuron differentiation. L-type channels, which support the depolarization-induced calcium influx in neurons from the very early developmental stages, are functionally restricted to the somatodendritic compartment throughout neuronal development and play a crucial role in supporting neurite outgrowth at early developmental stages. N-type channels, which start contributing at later neuronal differentiation stages (3-4 DIV), are also functionally expressed in the axons of immature neurons. At this developmental stage preceding synaptogenesis, N-type (but not L-type) channels are involved in controlling synaptic vesicle recycling. It is only at later developmental stages (10-12 DIV), when the neurons have established a clear axodendritic polarity and form synaptic contacts, that N-type channels are progressively excluded from the axon. Electrophysiological recordings of single neurons growing in microislands revealed that synaptic maturation coincides with a progressive increase in N-type channels in the somatodendritic region and a progressive decrease in the N-type channels supporting glutamate release from the presynaptic terminal. These results indicate that L-type and N-type calcium channels undergo dynamic, developmentally regulated rearrangements in regional distribution and function and also suggest that different mechanisms may be involved in the sorting and/or stabilization of these two types of channels in different plasma membrane domains during neuronal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / metabolism*
  • Calcium Channels, N-Type / metabolism*
  • Calcium Signaling / drug effects
  • Cell Differentiation
  • Cells, Cultured
  • Hippocampus / cytology
  • Hippocampus / embryology*
  • Hippocampus / metabolism*
  • Immunohistochemistry
  • Neurons / cytology
  • Neurons / metabolism*
  • Nifedipine / pharmacology
  • Patch-Clamp Techniques
  • Rats
  • Synaptic Vesicles / metabolism
  • omega-Conotoxin GVIA / pharmacology

Substances

  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • omega-Conotoxin GVIA
  • Nifedipine

Grant support