Shear Force Modulates the Activity of Acid-sensing Ion Channels at Low PH or in the Presence of Non-proton Ligands

Overview

Journal Sci Rep

Specialty Science

Date 2019 May 3

PMID 31043630

Citations 10

Authors

Daniel Barth

Martin Fronius

Affiliations

Soon will be listed here.

Abstract

Acid-sensing ion channels (ASICs) belong to the degenerin/epithelial sodium channel protein family that form mechanosensitive ion channels. Evidence as to whether or not ASICs activity is directly modulated by mechanical force is lacking. Human ASICs (hASIC1, hASIC2a and hASIC3a) were heterologously expressed as homomeric channels in Xenopus oocytes and two-electrode voltage-clamp recordings were performed. hASIC3a was expressed in HEK-293 cells and currents measured by whole-cell patch-clamp recordings. ASIC currents in response to shear force (SF) were measured at pH 7.4, acidic pH, or in the presence of non-proton ligands at pH 7.4. SF was applied via a fluid stream generated through a pressurized perfusion system. No effect was observed at pH 7.4. Increased transient currents for each homomeric channel were observed when elevated SF was applied in conjunction with acidic pH (6.0-4.0). The sustained current was not (hASIC2a) or only slightly increased (hASIC1 and hASIC3a). SF-induced effects were not seen in water injected oocytes and were blocked by amiloride. Non-proton ligands activated a persistent current in hASIC1 and cASIC1 (MitTx) and hASIC3a (GMQ) at pH 7.4. Here SF caused a further current increase. Results suggest that ASICs do have an intrinsic ability to respond to mechanical force, supporting their role as mechanosensors in certain local environments.

Citing Articles

Epithelial Na Channels Function as Extracellular Sensors.

Kashlan O, Wang X, Sheng S, Kleyman T Compr Physiol. 2024; 14(2):1-41.

PMID: 39109974 PMC: 11309579. DOI: 10.1002/cphy.c230015.

Proton-sensing ion channels, GPCRs and calcium signaling regulated by them: implications for cancer.

Ji R, Chang L, An C, Zhang J Front Cell Dev Biol. 2024; 12:1326231.

PMID: 38505262 PMC: 10949864. DOI: 10.3389/fcell.2024.1326231.

Acid-Sensing Ion Channels' Immunoreactivity in Nerve Profiles and Glomus Cells of the Human Carotid Body.

Martinez-Barbero G, Garcia-Mesa Y, Cobo R, Cuendias P, Martin-Biedma B, Garcia-Suarez O Int J Mol Sci. 2023; 24(24).

PMID: 38138991 PMC: 10743051. DOI: 10.3390/ijms242417161.

Mechanosensitive Ion Channels: Their Physiological Importance and Potential Key Role in Cancer.

Otero-Sobrino A, Blanco-Carlon P, Navarro-Aguadero M, Gallardo M, Martinez-Lopez J, Velasco-Estevez M Int J Mol Sci. 2023; 24(18).

PMID: 37762011 PMC: 10530364. DOI: 10.3390/ijms241813710.

Function and phylogeny support the independent evolution of an ASIC-like Deg/ENaC channel in the Placozoa.

Elkhatib W, Yanez-Guerra L, Mayorova T, Currie M, Singh A, Perera M Commun Biol. 2023; 6(1):951.

PMID: 37723223 PMC: 10507113. DOI: 10.1038/s42003-023-05312-0.

References

Paukert M, Chen X, Polleichtner G, Schindelin H, Grunder S . Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a. J Biol Chem. 2007; 283(1):572-581. DOI: 10.1074/jbc.M706811200. View

Althaus M, Bogdan R, Clauss W, Fronius M . Mechano-sensitivity of epithelial sodium channels (ENaCs): laminar shear stress increases ion channel open probability. FASEB J. 2007; 21(10):2389-99. DOI: 10.1096/fj.06-7694com. View

Vitzthum C, Clauss W, Fronius M . Mechanosensitive activation of CFTR by increased cell volume and hydrostatic pressure but not shear stress. Biochim Biophys Acta. 2015; 1848(11 Pt A):2942-51. DOI: 10.1016/j.bbamem.2015.09.009. View

Springauf A, Grunder S . An acid-sensing ion channel from shark (Squalus acanthias) mediates transient and sustained responses to protons. J Physiol. 2010; 588(Pt 5):809-20. PMC: 2834940. DOI: 10.1113/jphysiol.2009.182931. View

Babini E, Paukert M, Geisler H, 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. 2002; 277(44):41597-603. DOI: 10.1074/jbc.M205877200. View

Sanchez-Freire V, Blanchard M, Burkhard F, Kessler T, Kellenberger S, Monastyrskaya K . Acid-sensing channels in human bladder: expression, function and alterations during bladder pain syndrome. J Urol. 2011; 186(4):1509-16. DOI: 10.1016/j.juro.2011.05.047. View

Hoagland E, Sherwood T, Lee K, Walker C, Askwith C . Identification of a calcium permeable human acid-sensing ion channel 1 transcript variant. J Biol Chem. 2010; 285(53):41852-62. PMC: 3009913. DOI: 10.1074/jbc.M110.171330. View

Katta S, Krieg M, Goodman M . Feeling force: physical and physiological principles enabling sensory mechanotransduction. Annu Rev Cell Dev Biol. 2015; 31:347-71. DOI: 10.1146/annurev-cellbio-100913-013426. View

Bohlen C, Chesler A, Sharif-Naeini R, Medzihradszky K, Zhou S, King D . A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain. Nature. 2011; 479(7373):410-4. PMC: 3226747. DOI: 10.1038/nature10607. View

10.

Maroto R, Raso A, Wood T, Kurosky A, Martinac B, Hamill O . TRPC1 forms the stretch-activated cation channel in vertebrate cells. Nat Cell Biol. 2005; 7(2):179-85. DOI: 10.1038/ncb1218. View

11.

Sherwood T, Frey E, Askwith C . Structure and activity of the acid-sensing ion channels. Am J Physiol Cell Physiol. 2012; 303(7):C699-710. PMC: 3469599. DOI: 10.1152/ajpcell.00188.2012. View

12.

Loukin S, Zhou X, Su Z, Saimi Y, Kung C . Wild-type and brachyolmia-causing mutant TRPV4 channels respond directly to stretch force. J Biol Chem. 2010; 285(35):27176-27181. PMC: 2930716. DOI: 10.1074/jbc.M110.143370. View

13.

Omerbasic D, Schuhmacher L, Bernal Sierra Y, Smith E, Lewin G . ASICs and mammalian mechanoreceptor function. Neuropharmacology. 2014; 94:80-6. DOI: 10.1016/j.neuropharm.2014.12.007. View

14.

Drummond H, Grifoni S, Jernigan N . A new trick for an old dogma: ENaC proteins as mechanotransducers in vascular smooth muscle. Physiology (Bethesda). 2008; 23:23-31. DOI: 10.1152/physiol.00034.2007. View

15.

Deval E, Gasull X, Noel J, Salinas M, Baron A, Diochot S . Acid-sensing ion channels (ASICs): pharmacology and implication in pain. Pharmacol Ther. 2010; 128(3):549-58. DOI: 10.1016/j.pharmthera.2010.08.006. View

16.

Page A, Brierley S, Martin C, Price M, Symonds E, Butler R . Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function. Gut. 2005; 54(10):1408-15. PMC: 1774697. DOI: 10.1136/gut.2005.071084. View

17.

Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M . A proton-gated cation channel involved in acid-sensing. Nature. 1997; 386(6621):173-7. DOI: 10.1038/386173a0. View

18.

Jasti J, Furukawa H, Gonzales E, Gouaux E . Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. Nature. 2007; 449(7160):316-23. DOI: 10.1038/nature06163. View

19.

Kessler S, Clauss W, Gunther A, Kummer W, Fronius M . Expression and functional characterization of P2X receptors in mouse alveolar macrophages. Pflugers Arch. 2011; 462(3):419-30. DOI: 10.1007/s00424-011-0980-z. View

20.

Lingueglia E . Acid-sensing ion channels in sensory perception. J Biol Chem. 2007; 282(24):17325-9. DOI: 10.1074/jbc.R700011200. View