Voltage-gated ion channels in the axon initial segment of human cortical pyramidal cells and their relationship with chandelier cells.
The axon initial segment (AIS) of pyramidal cells is a critical region for the generation of action potentials and for the control of pyramidal cell activity. Here we show that Na+ and K+ voltage-gated channels, together with other molecules involved in the localization of ion channels, are distributed asymmetrically in the AIS of pyramidal cells situated in the human temporal neocortex. There is a high density of Na+ channels distributed along the length of the AIS together with the associated proteins spectrin betaIV and ankyrin G. In contrast, Kv1.2 channels are associated with the adhesion molecule Caspr2, and they are mostly localized to the distal region of the AIS. In general, the distal region of the AIS is targeted by the GABAergic axon terminals of chandelier cells, whereas the proximal region is innervated, mostly by other types of GABAergic interneurons. We suggest that this molecular segregation and the consequent regional specialization of the GABAergic input to the AIS of pyramidal cells may have important functional implications for the control of pyramidal cell activity.
Departamento de Biología Celular, Universidad Complutense de Madrid, Jose Antonio Novais 2, 28040 Madrid, Spain.
Maria Carmen
MC
Inda
Javier
J
DeFelipe
Alberto
A
Muñoz
D000328:Adult; D017487:Ankyrins / Q000032:analysis / Q000378:metabolism; D001369:Axons / Q000737:chemistry* / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D051663:Kv1.2 Potassium Channel / Q000032:analysis / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000032:analysis* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000737:chemistry; D017966:Pyramidal Cells / Q000737:chemistry* / Q000378:metabolism; D011901:Ranvier's Nodes / Q000737:chemistry; D015222:Sodium Channels / Q000032:analysis* / Q000378:metabolism; D013049:Spectrin / Q000032:analysis / Q000378:metabolism
C490613:ANK3 protein, human; D017487:Ankyrins; C403049:CNTNAP2 protein, human; D050485:GABA Plasma Membrane Transport Proteins; D051663:Kv1.2 Potassium Channel; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels; C417303:betaIV spectrin; D013049:Spectrin