The axon initial segment (AIS) is highly enriched in the structural proteins ankyrin G and βIV-spectrin, the pore-forming (α) subunits of voltage-gated sodium (Nav) channels, and functional Nav channels, and is critical for the initiation of action potentials. We previously reported that FGF14, a member of the intracellular FGF (iFGF) sub-family, is expressed in cerebellar Purkinje neurons and that the targeted inactivation of Fgf14 in mice (Fgf14(-/-)) results in markedly reduced Purkinje neuron excitability. Here, we demonstrate that FGF14 immunoreactivity is high in the AIS of Purkinje neurons and is distributed in a decreasing, proximal to distal, gradient. This pattern is evident early in the postnatal development of Purkinje neurons and is also observed in many other types of central neurons. In (Scn8a(med)) mice, which are deficient in expression of the Nav1.6 α subunit, FGF14 immunoreactivity is markedly increased and expanded in the Purkinje neuron AIS, in parallel with increased expression of the Nav1.1 (Scn1a) α subunit and expanded expression of βIV-spectrin. Although Nav1.1, FGF14, and βIV-spectrin are affected, ankyrin G immunoreactivity at the AIS of Scn8a(med) and wild type (WT) Purkinje neurons was not significantly different. In Fgf14(-/-) Purkinje neurons, βIV-spectrin and ankyrin G immunoreactivity at the AIS were also similar to WT Purkinje neurons, although both the Nav1.1 and Nav1.6 α subunits are modestly, but significantly (p<0.005), reduced within sub-domains of the AIS, changes that may contribute to the reduced excitability of Fgf14(-/-) Purkinje neurons.
Pubmed ID: 23891806 RIS Download
Mesh terms: Animals | Ankyrins | Axons | Cells, Cultured | Fibroblast Growth Factors | Mice | Mice, Inbred C57BL | Mice, Knockout | NAV1.1 Voltage-Gated Sodium Channel | NAV1.6 Voltage-Gated Sodium Channel | Protein Transport | Purkinje Cells | Spectrin
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
An Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.
toolView all literature mentions