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Differential targeting of the L‐type Ca 2+ channel α 1C (Ca V 1.2) to synaptic and extrasynaptic compartments in hippocampal neurons
Author(s) -
Obermair Gerald J.,
Szabo Zsolt,
Bourinet Emmanuel,
Flucher Bernhard E.
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.0953-816x.2004.03272.x
Subject(s) - glutamatergic , neuroscience , gabaergic , postsynaptic potential , hippocampal formation , biology , axon , dendritic spine , microbiology and biotechnology , glutamate receptor , chemistry , inhibitory postsynaptic potential , receptor , biochemistry
In central nervous system neurons L‐type Ca 2+ channels are involved in developmental processes, the integration and conduction of postsynaptic electric activity and synaptic plasticity. However, little is known about the channel isoforms underlying each of these functions or about the exact localization and targeting properties of the major L‐type channel isoform α 1C (Ca V 1.2) in neurons. We addressed these questions using high‐resolution immunofluorescence analysis of the endogenous α 1C and epitope‐tagged recombinant channel isoforms expressed in mouse hippocampal neurons. Endogenous α 1C and surface‐expressed hemagglutinin (HA)‐tagged α 1C ‐HA were localized in small clusters distributed between the axon initial segment and the apical branches of the dendritic tree. The average cluster size was estimated to be eight channels per α 1C ‐HA cluster. Analysis of the subcellular localization of α 1C ‐HA clusters relative to known synaptic markers suggested the existence of two distinct populations of α 1C clusters, extrasynaptic and synaptic, the latter associated with glutamatergic synapses in dendritic spines. Both glutamatergic and GABAergic neurons expressed α 1C in the soma and dendrites. In contrast to the N‐type channel GFP‐α 1B , GFP‐α 1C was excluded from distal axons and nerve terminals of mature neurons. In developing neurons, however, α 1C and α 1C ‐HA were robustly expressed in the growth cone, indicating that specific targeting properties of neuronal compartments change during differentiation. Synaptic and extrasynaptic localizations of α 1C correspond to putative roles of L‐type Ca 2+ currents in synaptic modulation and in the propagation of dendritic Ca 2+ spikes, respectively. The transiently expressed α 1C in the growth cone may be involved in neurite extension and axonal pathfinding.