Voltage-gated ion channels in the axon initial segment of human cortical pyramidal cells and their relationship with chandelier cells

Abstract

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 ؉ voltagegated 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 ␤IV 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.inhibition ͉ interneurons ͉ neocortex

Selective control of cortical axonal spikes by a slowly inactivating K + current

“…Together, these results implicate K ϩ channels containing Kv1.2 subunits, either in a heteromeric or homomeric mixture (11,36,37) are the mediators of the D-current responsible for axonal spike repolarization. Immunocytochemical studies reveal the prominent expression of Kv 1.2 channels in axons and axonal terminal fields throughout the brain (6,11,38,39). In the neocortex, Kv1.2 is of particularly high density in the more distal portions of the axon initial segment of cortical pyramidal cells (6).…”

“…The answer to this question is largely unknown. Immunocytochemical studies indicate that pyramidal cell axons contain a high density of transient and persistent Na ϩ currents, particularly in the axon initial segment and nodes of Ranvier (6)(7)(8) and at least Kv1.2 ␣-subunit containing K ϩ channels (6). In other preparations, Kv1.1, 1.2, and 1.6 ␣-subunits contribute to the formation of low-threshold K ϩ channels that are important in determining axonal excitability and axonal spike duration (9)(10)(11)(12).…”

Shining a light on CNTNAP2: complex functions to complex disorders

“…63,64 Formation of this complex is mediated by Protein 4.1B binding to the intracellular portion of CASPR2 and is required for the clustering of voltage-gated potassium channels at juxtaparanodes. 65 These channels are involved in the rapid, saltatory conduction of nerve impulses, 66 and individuals from the CDFE cohort (with homozygous CNTNAP2 mutations) display reduced potassium channel (K v 1.1) localisation in hippocampal axons.…”

Nav1.1 Localizes to Axons of Parvalbumin-Positive Inhibitory Interneurons: A Circuit Basis for Epileptic Seizures in Mice Carrying anScn1aGene Mutation

“…Examination of Na v 1.1 colocalization with ␤IV-spectrin, which is associated with ankyrin-G and specifically clustered at AISs and nodes of Ranvier (Berghs et al, 2000;Komada and Soriano, 2002;Inda et al, 2006), revealed that the Na v 1.1-immunoreactive portions of the nerve fibers were the ␤IV-spectrin-immunoreactive AISs of PV interneurons (Fig. 5Ba,Bb,Bd).…”