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

Naomi A K Hanemaaijer, Marko A Popovic, Xante Wilders, Sara Grasman, Oriol Pavón Arocas, Maarten H P Kole

Research output: Contribution to journal/periodicalArticleScientificpeer-review

14 Citations (Scopus)
146 Downloads (Pure)


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 5 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.

Original languageEnglish
Article numbere54566
Publication statusPublished - 08 Mar 2020


Dive into the research topics of 'Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling'. Together they form a unique fingerprint.

Cite this