Slowing of the Time Course of Acidification Decreases the Acid-Sensing Ion Channel 1a Current Amplitude and Modulates Action Potential Firing in Neurons

Détails

Ressource 1Télécharger: Alijevic_2020fncel-14-00041.pdf (2624.47 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_46E0F89C36DB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Slowing of the Time Course of Acidification Decreases the Acid-Sensing Ion Channel 1a Current Amplitude and Modulates Action Potential Firing in Neurons
Périodique
Frontiers in Cellular Neuroscience
Auteur(s)
Alijevic Omar, Bignucolo Olivier, Hichri Echrak, Peng Zhong, Kucera Jan P., Kellenberger Stephan
ISSN
1662-5102
Statut éditorial
Publié
Date de publication
28/02/2020
Volume
14
Langue
anglais
Résumé
Acid-sensing ion channels (ASICs) are H+-activated neuronal Na+ channels. They are involved in fear behavior, learning, neurodegeneration after ischemic stroke and in pain sensation. ASIC activation has so far been studied only with fast pH changes, although the pH changes associated with many roles of ASICs are slow. It is currently not known whether slow pH changes can open ASICs at all. Here, we investigated to which extent slow pH changes can activate ASIC1a channels and induce action potential signaling. To this end, ASIC1a current amplitudes and charge transport in transfected Chinese hamster ovary cells, and ASIC-mediated action potential signaling in cultured cortical neurons were measured in response to defined pH ramps of 1-40 s duration from pH7.4 to pH6.6 or 6.0. A kinetic model of the ASIC1a current was developed and integrated into the Hodgkin-Huxley action potential model. Interestingly, whereas the ASIC1a current amplitude decreased with slower pH ramps, action potential firing was higher upon intermediate than fast acidification in cortical neurons. Indeed, fast pH changes (<4 s) induced short action potential bursts, while pH changes of intermediate speed (4-10 s) induced longer bursts. Slower pH changes (>10 s) did in many experiments not generate action potentials. Computer simulations corroborated these observations. We provide here the first description of ASIC function in response to defined slow pH changes. Our study shows that ASIC1a currents, and neuronal activity induced by ASIC1a currents, strongly depend on the speed of pH changes. Importantly, with pH changes that take >10 s to complete, ASIC1a activation is inefficient. Therefore, it is likely that currently unknown modulatory mechanisms allow ASIC activity in situations such as ischemia and inflammation.
Mots-clé
Cellular and Molecular Neuroscience
Pubmed
Open Access
Oui
Financement(s)
Fonds national suisse / 310030_184707
Fonds national suisse / 31003A_172968
Création de la notice
31/03/2020 18:51
Dernière modification de la notice
28/04/2020 7:08
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