ATP Release Channels

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Mar 15

PMID 29534490

Citations 94

Authors

Akiyuki Taruno

Affiliations

Soon will be listed here.

Abstract

Adenosine triphosphate (ATP) has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1), volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR) anion channels), and maxi-anion channels (MACs). Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

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References

Chiu Y, Jin X, Medina C, Leonhardt S, Kiessling V, Bennett B . A quantized mechanism for activation of pannexin channels. Nat Commun. 2017; 8:14324. PMC: 5290276. DOI: 10.1038/ncomms14324. View

Huckstepp R, id Bihi R, Eason R, Spyer K, Dicke N, Willecke K . Connexin hemichannel-mediated CO2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity. J Physiol. 2010; 588(Pt 20):3901-20. PMC: 3000581. DOI: 10.1113/jphysiol.2010.192088. View

Romanov R, Bystrova M, Rogachevskaya O, Sadovnikov V, Shestopalov V, Kolesnikov S . The ATP permeability of pannexin 1 channels in a heterologous system and in mammalian taste cells is dispensable. J Cell Sci. 2012; 125(Pt 22):5514-23. PMC: 3561859. DOI: 10.1242/jcs.111062. View

Tordoff M, Ellis H, Aleman T, Downing A, Marambaud P, Foskett J . Salty taste deficits in CALHM1 knockout mice. Chem Senses. 2014; 39(6):515-28. PMC: 4064958. DOI: 10.1093/chemse/bju020. View

Shimizu T, Numata T, Okada Y . A role of reactive oxygen species in apoptotic activation of volume-sensitive Cl(-) channel. Proc Natl Acad Sci U S A. 2004; 101(17):6770-3. PMC: 404120. DOI: 10.1073/pnas.0401604101. View

Dreses-Werringloer U, Lambert J, Vingtdeux V, Zhao H, Vais H, Siebert A . A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk. Cell. 2008; 133(7):1149-61. PMC: 2577842. DOI: 10.1016/j.cell.2008.05.048. View

Abraham E, Prat A, Gerweck L, Seneveratne T, Arceci R, Kramer R . The multidrug resistance (mdr1) gene product functions as an ATP channel. Proc Natl Acad Sci U S A. 1993; 90(1):312-6. PMC: 45650. DOI: 10.1073/pnas.90.1.312. View

Yegutkin G . Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade. Biochim Biophys Acta. 2008; 1783(5):673-94. DOI: 10.1016/j.bbamcr.2008.01.024. View

Locovei S, Scemes E, Qiu F, Spray D, Dahl G . Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex. FEBS Lett. 2007; 581(3):483-8. PMC: 1868681. DOI: 10.1016/j.febslet.2006.12.056. View

10.

Bao L, Locovei S, Dahl G . Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett. 2004; 572(1-3):65-8. DOI: 10.1016/j.febslet.2004.07.009. View

11.

Bell P, Lapointe J, Sabirov R, Hayashi S, Peti-Peterdi J, Manabe K . Macula densa cell signaling involves ATP release through a maxi anion channel. Proc Natl Acad Sci U S A. 2003; 100(7):4322-7. PMC: 153091. DOI: 10.1073/pnas.0736323100. View

12.

Ohshima Y, Tsukimoto M, Takenouchi T, Harada H, Suzuki A, Sato M . gamma-Irradiation induces P2X(7) receptor-dependent ATP release from B16 melanoma cells. Biochim Biophys Acta. 2009; 1800(1):40-6. DOI: 10.1016/j.bbagen.2009.10.008. View

13.

Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne D . P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci. 2001; 21(15):5670-7. PMC: 6762653. View

14.

Nakagomi H, Yoshiyama M, Mochizuki T, Miyamoto T, Komatsu R, Imura Y . Urothelial ATP exocytosis: regulation of bladder compliance in the urine storage phase. Sci Rep. 2016; 6:29761. PMC: 4944198. DOI: 10.1038/srep29761. View

15.

Qiu Z, Dubin A, Mathur J, Tu B, Reddy K, Miraglia L . SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel. Cell. 2014; 157(2):447-458. PMC: 4023864. DOI: 10.1016/j.cell.2014.03.024. View

16.

Tordoff M, Aleman T, Ellis H, Ohmoto M, Matsumoto I, Shestopalov V . Normal Taste Acceptance and Preference of PANX1 Knockout Mice. Chem Senses. 2015; 40(7):453-9. PMC: 4635636. DOI: 10.1093/chemse/bjv025. View

17.

Wang E, Lee J, Ruiz W, Balestreire E, von Bodungen M, Barrick S . ATP and purinergic receptor-dependent membrane traffic in bladder umbrella cells. J Clin Invest. 2005; 115(9):2412-22. PMC: 1187935. DOI: 10.1172/JCI24086. View

18.

Peti-Peterdi J, Morishima S, Bell P, Okada Y . Two-photon excitation fluorescence imaging of the living juxtaglomerular apparatus. Am J Physiol Renal Physiol. 2002; 283(1):F197-201. DOI: 10.1152/ajprenal.00356.2001. View

19.

Droogmans G, Prenen J, Eggermont J, Voets T, Nilius B . Voltage-dependent block of endothelial volume-regulated anion channels by calix[4]arenes. Am J Physiol. 1998; 275(3):C646-52. DOI: 10.1152/ajpcell.1998.275.3.C646. View

20.

Liu H, Sabirov R, Okada Y . Oxygen-glucose deprivation induces ATP release via maxi-anion channels in astrocytes. Purinergic Signal. 2008; 4(2):147-54. PMC: 2377326. DOI: 10.1007/s11302-007-9077-8. View