Molecular determinants of ASIC1 modulation by divalent cations.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
28 Jan 2024
Historique:
received: 07 09 2023
accepted: 24 01 2024
medline: 29 1 2024
pubmed: 29 1 2024
entrez: 28 1 2024
Statut: epublish

Résumé

Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the nervous system. ASIC gating is modulated by divalent cations as well as small molecules; however, the molecular determinants of gating modulation by divalent cations are not well understood. Previously, we identified two small molecules that bind to ASIC1a at a novel site in the acidic pocket and modulate ASIC1 gating in a manner broadly resembling divalent cations, raising the possibility that these small molecules may help to illuminate the molecular determinants of gating modulation by divalent cations. Here, we examined how these two groups of modulators might interact as well as mutational effects on ASIC1a gating and its modulation by divalent cations. Our results indicate that binding of divalent cations to an acidic pocket site plays a key role in gating modulation of the channel.

Identifiants

pubmed: 38282035
doi: 10.1038/s41598-024-52845-3
pii: 10.1038/s41598-024-52845-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2320

Informations de copyright

© 2024. The Author(s).

Références

Krishtal, O. A. & Pidoplichko, V. I. A receptor for protons in the nerve cell membrane. Neuroscience 5, 2325–2327 (1980).
doi: 10.1016/0306-4522(80)90149-9 pubmed: 6970348
Waldmann, R., Champigny, G., Bassilana, F., Heurteaux, C. & Lazdunski, M. A proton-gated cation channel involved in acid-sensing. Nature 386, 173–177 (1997).
doi: 10.1038/386173a0 pubmed: 9062189
Jasti, J., Furukawa, H., Gonzales, E. B. & Gouaux, E. Structure of acid-sensing ion channel 1 at 1.9 Å resolution and low pH. Nature 449, 316–323 (2007).
doi: 10.1038/nature06163 pubmed: 17882215
Sherwood, T. W., Frey, E. N. & Askwith, C. C. Structure and activity of the acid-sensing ion channels. Am. J. Physiol. Cell Physiol. 303, C699-710 (2012).
doi: 10.1152/ajpcell.00188.2012 pubmed: 22843794 pmcid: 3469599
Wemmie, J. A. et al. The acid activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. Neuron 34, 463–477 (2002).
doi: 10.1016/S0896-6273(02)00661-X pubmed: 11988176
Du, J. et al. Protons and ASICs are a neurotransmitter/receptor pair that regulates synaptic plasticity in the lateral amygdala. Proc. Natl. Acad. Sci. U.S.A. 111, 8961–8966 (2014).
doi: 10.1073/pnas.1407018111 pubmed: 24889629 pmcid: 4066526
Kreple, C. J. et al. Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity. Nat. Neurosci. 8, 1083–1091 (2014).
doi: 10.1038/nn.3750
González-Inchauspe, C., Urbano, F. J., Di Guilmi, M. N. & Uchitel, O. D. Acid-sensing ion channels activated by evoked released protons modulate synaptic transmission at the mouse calyx of Held synapse. J. Neurosci. 37, 2589–2599 (2017).
doi: 10.1523/JNEUROSCI.2566-16.2017 pubmed: 28159907 pmcid: 6596635
Xiong, Z. G. et al. Neuroprotection in ischemia: Blocking calcium-permeable acid-sensing ion channels. Cell 118, 687–698 (2004).
doi: 10.1016/j.cell.2004.08.026 pubmed: 15369669
Friese, M. A. et al. Acid-sensing ion channel-1 contributes toaxonal degeneration in autoimmune inflammation of the central nervous system. Nat. Med. 13, 1483–1489 (2007).
doi: 10.1038/nm1668 pubmed: 17994101
Pignataro, G., Simon, R. P. & Xiong, Z. G. Prolonged activation of ASIC1a and the time window for neuroprotection in cerebral ischaemia. Brain 130, 151–158 (2007).
doi: 10.1093/brain/awl325 pubmed: 17114797
Duan, B. et al. Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. J. Neurosci. 31, 2101–2112 (2011).
doi: 10.1523/JNEUROSCI.4351-10.2011 pubmed: 21307247 pmcid: 3101878
McCarthy, C. A., Rash, L. D., Chassagnon, I. R., King, G. F. & Widdop, R. E. PcTx1 affords neuroprotection in a conscious model of stroke in hypertensive rats via selective inhibition of ASIC1a. Neuropharmacology 99, 650–657 (2015).
doi: 10.1016/j.neuropharm.2015.08.040 pubmed: 26320544
Chen, C. C. et al. A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc. Natl. Acad. Sci. U.S.A. 99, 8992–8997 (2002).
doi: 10.1073/pnas.122245999 pubmed: 12060708 pmcid: 124411
Sluka, K. A. et al. Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain 106, 229–239 (2003).
doi: 10.1016/S0304-3959(03)00269-0 pubmed: 14659506
de Weille, J. & Bassilana, F. Dependence of the acid-sensitive ion channel, ASIC1a, on extracellular Ca
doi: 10.1016/S0006-8993(01)02345-9 pubmed: 11334808
Babini, E., Paukert, M., Geisler, H. S. & Grunder, S. Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1). J. Biol. Chem. 277, 41597–41603 (2002).
doi: 10.1074/jbc.M205877200 pubmed: 12198124
Immke, D. C. & McCleskey, E. W. Protons open acid-sensing ion channels by catalyzing relief of Ca
doi: 10.1016/S0896-6273(02)01130-3 pubmed: 12526774
Paukert, M., Babini, E., Pusch, M. & Gründer, S. Identification of the Ca
doi: 10.1085/jgp.200308973 pubmed: 15452199 pmcid: 2233906
Zhang, P., Sigworth, F. J. & Canessa, C. M. Gating of acid-sensitive ion channel-1: Release of Ca
doi: 10.1085/jgp.200509396 pubmed: 16418400 pmcid: 2151491
Zuo, Z. et al. Identification of a unique Ca
doi: 10.1038/s41467-018-04424-0 pubmed: 29802295 pmcid: 5970173
Yoder, N. & Gouaux, E. Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography. PLoS One 13, e0202134. https://doi.org/10.1371/journal.pone.0202134 (2018).
doi: 10.1371/journal.pone.0202134 pubmed: 30157194 pmcid: 6114778
Liu, Y. et al. Molecular mechanism and structural basis of small-molecule modulation of the gating of acid-sensing ion channel 1. Commun. Biol. 4, 174. https://doi.org/10.1038/s42003-021-01678-1 (2021).
doi: 10.1038/s42003-021-01678-1 pubmed: 33564124 pmcid: 7873226
Yoder, N., Yoshioka, C. & Gouaux, E. Gating mechanisms of acid-sensing ion channels. Nature 555, 397–401 (2018).
doi: 10.1038/nature25782 pubmed: 29513651 pmcid: 5966032
Chen, X. & Gründer, S. Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a. J. Physiol. 579, 657–670 (2007).
doi: 10.1113/jphysiol.2006.120733 pubmed: 17204502 pmcid: 2151377
Borg, B. C. et al. Mechanism and site of action of big dynorphin on ASIC1a. Proc. Natl Acad. Sci. U.S.A. 117, 7447–7454 (2020).
doi: 10.1073/pnas.1919323117 pubmed: 32165542 pmcid: 7132280
Leisle, L. et al. Dynorphin neuropeptides decrease apparent proton affinity of ASIC1a by occluding the acidic pocket. J. Med. Chem. 64, 13299–13311 (2021).
doi: 10.1021/acs.jmedchem.1c00447 pubmed: 34461722
Gonzales, E. B., Kawate, T. & Gouaux, E. Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. Nature 460, 599–604 (2009).
doi: 10.1038/nature08218 pubmed: 19641589 pmcid: 2845979
Baconguis, I. & Gouaux, E. Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes. Nature 489, 400–405 (2012).
doi: 10.1038/nature11375 pubmed: 22842900 pmcid: 3725952

Auteurs

Yi Liu (Y)

Neuroscience Discovery, Janssen Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA, 92121, USA.

Jichun Ma (J)

Therapeutics Discovery, Janssen Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA, 19477, USA.

Renee L DesJarlais (RL)

Therapeutics Discovery, Janssen Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA, 19477, USA.

Rebecca Hagan (R)

Neuroscience Discovery, Janssen Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA, 92121, USA.

Jason Rech (J)

Therapeutics Discovery, Janssen Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA, 92121, USA.

Changlu Liu (C)

Neuroscience Discovery, Janssen Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA, 92121, USA.

Robyn Miller (R)

Therapeutics Discovery, Janssen Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA, 19477, USA.

Jeffrey Schoellerman (J)

Neuroscience Discovery, Janssen Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA, 92121, USA.

Jinquan Luo (J)

Therapeutics Discovery, Janssen Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA, 19477, USA.

Michael Letavic (M)

Therapeutics Discovery, Janssen Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA, 92121, USA.

Bruce Grasberger (B)

Therapeutics Discovery, Janssen Research & Development, L.L.C., Welsh & McKean Roads, P.O. Box 776, Spring House, PA, 19477, USA.

Michael P Maher (MP)

Neuroscience Discovery, Janssen Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA, 92121, USA. mmaher1@its.jnj.com.

Classifications MeSH