Journal
JOURNAL OF NEUROSCIENCE
Volume 26, Issue 16, Pages 4289-4297Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4178-05.2006
Keywords
GABA(B1); Kir3; G-protein; coupled receptors; electron microscopy; immunocytochemistry; spillover
Categories
Funding
- NIDA NIH HHS [P50 DA011806, DA011806] Funding Source: Medline
- NIMH NIH HHS [MH61933, R01 MH061933] Funding Source: Medline
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G-protein-coupled inwardly rectifying K+ channels (Kir3 channels) coupled to metabotropic GABA(B) receptors are essential for the control of neuronal excitation. To determine the distribution of Kir3 channels and their spatial relationship to GABAB receptors on hippocampal pyramidal cells, we used a high-resolution immunocytochemical approach. Immunoreactivity for the Kir3.2 subunit was most abundant postsynaptically and localized to the extrasynaptic plasma membrane of dendritic shafts and spines of principal cells. Quantitative analysis of immunogold particles for Kir3.2 revealed an enrichment of the protein around putative glutamatergic synapses on dendritic spines, similar to that of GABA(B1). Consistent with this observation, a high degree of coclustering of Kir3.2 and GABAB1 was revealed around excitatory synapses by the highly sensitive SDS-digested freeze-fracture replica immunolabeling. In contrast, in dendritic shafts receptors and channels were found to be mainly segregated. These results suggest that Kir3.2-containing K+ channels on dendritic spines preferentially mediate the effect of GABA, whereas channels on dendritic shafts are likely to be activated by other neurotransmitters as well. Thus, Kir3 channels, localized to different subcellular compartments of hippocampal principal cells, appear to be differentially involved in synaptic integration in pyramidal cell dendrites.
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