Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling
Autor: | Oriol Pavón Arocas, Naomi A. K. Hanemaaijer, Sara Grasman, Maarten H. P. Kole, Xante Wilders, Marko Popovic |
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Přispěvatelé: | Netherlands Institute for Neuroscience (NIN) |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
node of Ranvier
QH301-705.5 Science chemistry.chemical_element Calcium General Biochemistry Genetics and Molecular Biology Calcium in biology axon initial segment Calcium imaging medicine Channel blocker Axon Biology (General) General Immunology and Microbiology Voltage-dependent calcium channel General Neuroscience Sodium channel General Medicine Axon initial segment calcium imaging medicine.anatomical_structure chemistry Biophysics Medicine sodium channel |
Zdroj: | eLife, Vol 9 (2020) eLife, 9:e54566. eLife Sciences Publications |
ISSN: | 2050-084X |
Popis: | 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+]ichanges were sensitive to the specific voltage-gated sodium (NaV) channel blocker tetrodotoxin. Consistent with the conjecture that Ca2+enters through the NaVchannel pore, the optically resolvedICain the axon initial segment overlapped with the activation kinetics of NaVchannels and heterologous expression of NaV1.2 in HEK-293 cells revealed a tetrodotoxin-sensitive [Ca2+]irise. Finally, computational simulations predicted that axonal [Ca2+]itransients reflect a 0.4% Ca2+conductivity of NaVchannels. The findings indicate that Ca2+permeation through NaVchannels provides a submillisecond rapid entry route in NaV-enriched domains of mammalian axons. |
Databáze: | OpenAIRE |
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