Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling

© 2020, Hanemaaijer et al..

Calcium ions (Ca2+) are essential for many cellular signaling mechanisms and enter the cytosol mostly through voltage-gated calcium channels. Here, using high-speed Ca2+ imaging up to 20 kHz in the rat layer five pyramidal neuron axon we found that activity-dependent intracellular calcium concentration ([Ca2+]i) in the axonal initial segment was only partially dependent on voltage-gated calcium channels. Instead, [Ca2+]i changes were sensitive to the specific voltage-gated sodium (NaV) channel blocker tetrodotoxin. Consistent with the conjecture that Ca2+ enters through the NaV channel pore, the optically resolved ICa in the axon initial segment overlapped with the activation kinetics of NaV channels and heterologous expression of NaV1.2 in HEK-293 cells revealed a tetrodotoxin-sensitive [Ca2+]i rise. Finally, computational simulations predicted that axonal [Ca2+]i transients reflect a 0.4% Ca2+ conductivity of NaV channels. The findings indicate that Ca2+ permeation through NaV channels provides a submillisecond rapid entry route in NaV-enriched domains of mammalian axons.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

eLife - 9(2020) vom: 17. Juni

Sprache:

Englisch

Beteiligte Personen:

Hanemaaijer, Naomi Ak [VerfasserIn]
Popovic, Marko A [VerfasserIn]
Wilders, Xante [VerfasserIn]
Grasman, Sara [VerfasserIn]
Pavón Arocas, Oriol [VerfasserIn]
Kole, Maarten Hp [VerfasserIn]

Links:

Volltext

Themen:

4368-28-9
Axon initial segment
Calcium
Calcium imaging
Human
Journal Article
Neuroscience
Node of Ranvier
Rat
Research Support, Non-U.S. Gov't
SY7Q814VUP
Sodium channel
Tetrodotoxin
Voltage-Gated Sodium Channels

Anmerkungen:

Date Completed 14.04.2021

Date Revised 14.04.2021

published: Electronic

Citation Status MEDLINE

doi:

10.7554/eLife.54566

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM311318746