scholarly journals Voltage-gated potassium channels ensure action potential shape fidelity in distal axons

2020 ◽  
Author(s):  
Victoria Gonzalez Sabater ◽  
Mark Rigby ◽  
Juan Burrone

The initiation and propagation of the action potential (AP) along an axon allows neurons to convey information rapidly and across distant sites. Although AP properties have typically been characterised at the soma and proximal axon, the propagation of APs towards distal axonal domains of mammalian neurons remains limited. We used Genetically Encoded Voltage Indicators (GEVIs) to image APs simultaneously at different locations along the long axons of dissociated hippocampal neurons with sub-millisecond temporal resolution. We found that APs became sharper and showed remarkable fidelity as they traveled towards distal axons, even during a high frequency train. Blocking voltage-gated potassium channels (Kv) with 4-AP resulted in an increase in AP width in all compartments, which was stronger at distal locations and exacerbated during AP trains. We conclude that the higher levels of Kv channel activity in distal axons serves to sustain AP fidelity, conveying a reliable digital signal to presynaptic boutons.

2014 ◽  
Vol 106 (2) ◽  
pp. 119a
Author(s):  
Luca Sala ◽  
Bence Hegyi ◽  
Chiara Bartolucci ◽  
Claudia Altomare ◽  
Marcella Rocchetti ◽  
...  

2016 ◽  
Vol 113 (19) ◽  
pp. E2665-E2674 ◽  
Author(s):  
Juan Lorenzo Pablo ◽  
Chaojian Wang ◽  
Matthew M. Presby ◽  
Geoffrey S. Pitt

Clustering of voltage-gated sodium channels (VGSCs) within the neuronal axon initial segment (AIS) is critical for efficient action potential initiation. Although initially inserted into both somatodendritic and axonal membranes, VGSCs are concentrated within the axon through mechanisms that include preferential axonal targeting and selective somatodendritic endocytosis. How the endocytic machinery specifically targets somatic VGSCs is unknown. Here, using knockdown strategies, we show that noncanonical FGF13 binds directly to VGSCs in hippocampal neurons to limit their somatodendritic surface expression, although exerting little effect on VGSCs within the AIS. In contrast, homologous FGF14, which is highly concentrated in the proximal axon, binds directly to VGSCs to promote their axonal localization. Single-point mutations in FGF13 or FGF14 abrogating VGSC interaction in vitro cannot support these specific functions in neurons. Thus, our data show how the concerted actions of FGF13 and FGF14 regulate the polarized localization of VGSCs that supports efficient action potential initiation.


2013 ◽  
Vol 109 (6) ◽  
pp. 1514-1524 ◽  
Author(s):  
Raffaella Tonini ◽  
Teresa Ferraro ◽  
Marisol Sampedro-Castañeda ◽  
Anna Cavaccini ◽  
Martin Stocker ◽  
...  

In hippocampal pyramidal neurons, voltage-gated Ca2+ channels open in response to action potentials. This results in elevations in the intracellular concentration of Ca2+ that are maximal in the proximal apical dendrites and decrease rapidly with distance from the soma. The control of these action potential-evoked Ca2+ elevations is critical for the regulation of hippocampal neuronal activity. As part of Ca2+ signaling microdomains, small-conductance Ca2+-activated K+ (SK) channels have been shown to modulate the amplitude and duration of intracellular Ca2+ signals by feedback regulation of synaptically activated Ca2+ sources in small distal dendrites and dendritic spines, thus affecting synaptic plasticity in the hippocampus. In this study, we investigated the effect of the activation of SK channels on Ca2+ transients specifically induced by action potentials in the proximal processes of hippocampal pyramidal neurons. Our results, obtained by using selective SK channel blockers and enhancers, show that SK channels act in a feedback loop, in which their activation by Ca2+ entering mainly through L-type voltage-gated Ca2+ channels leads to a reduction in the subsequent dendritic influx of Ca2+. This underscores a new role of SK channels in the proximal apical dendrite of hippocampal pyramidal neurons.


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