Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling
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 concentrat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/54566 |
| _version_ | 1811181037885063168 |
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| author | Naomi AK Hanemaaijer Marko A Popovic Xante Wilders Sara Grasman Oriol Pavón Arocas Maarten HP Kole |
| author_facet | Naomi AK Hanemaaijer Marko A Popovic Xante Wilders Sara Grasman Oriol Pavón Arocas Maarten HP Kole |
| author_sort | Naomi AK Hanemaaijer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:12:43Z |
| format | Article |
| id | doaj.art-79f526a8462b4f43bbd8721c75d76901 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:43Z |
| publishDate | 2020-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-79f526a8462b4f43bbd8721c75d769012022-12-22T04:32:28ZengeLife Sciences Publications LtdeLife2050-084X2020-06-01910.7554/eLife.54566Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signalingNaomi AK Hanemaaijer0https://orcid.org/0000-0002-0329-5129Marko A Popovic1Xante Wilders2Sara Grasman3Oriol Pavón Arocas4https://orcid.org/0000-0001-5822-8858Maarten HP Kole5https://orcid.org/0000-0002-3883-5682Department of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, Netherlands; Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsDepartment of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, NetherlandsDepartment of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, NetherlandsDepartment of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, NetherlandsDepartment of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, NetherlandsDepartment of Axonal Signaling, Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, Netherlands; Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, NetherlandsCalcium 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.https://elifesciences.org/articles/54566axon initial segmentsodium channelcalcium imagingnode of Ranvier |
| spellingShingle | Naomi AK Hanemaaijer Marko A Popovic Xante Wilders Sara Grasman Oriol Pavón Arocas Maarten HP Kole Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling eLife axon initial segment sodium channel calcium imaging node of Ranvier |
| title | Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling |
| title_full | Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling |
| title_fullStr | Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling |
| title_full_unstemmed | Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling |
| title_short | Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling |
| title_sort | ca2 entry through nav channels generates submillisecond axonal ca2 signaling |
| topic | axon initial segment sodium channel calcium imaging node of Ranvier |
| url | https://elifesciences.org/articles/54566 |
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