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.
Highlights
Adenosine triphosphate (ATP) is abundantly present in the cytosol and used to power energy-consuming reactions, as the hydrolysis of ATP releases energy. It is known as the energy currency of cells. In addition to this classical cytosolic role, ATP has been established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission in numerous physiological and pathophysiological phenomena as it satisfies the criteria for extracellular ligands: production, release, receptors, and extracellular scavenging systems [1,2,3]
Ectonucleotidases are ubiquitously expressed in the plasma membranes and their active catalytic sites are exposed to the extracellular space to convert extracellular ATP to ADP, AMP, and adenosine [4,5]
ATP influx through an excised inside-out membrane patch detected by the luciferase/luciferin-based luminescence assay coincided with single-channel openings of connexin 43 (Cx43) hemichannels recorded by patch-clamp recordings
Summary
Adenosine triphosphate (ATP) is abundantly present in the cytosol and used to power energy-consuming reactions, as the hydrolysis of ATP releases energy It is known as the energy currency of cells. NIneltsh.eIpnretsheencpe roefspehnycseioolofgpichalylseivoellosgical levelsofofMMg2g+,2+th, ethmeamjoraitjoyriotfyAoTfPATmPolemcuolleescuexleisst eaxsisMt gaAs TMPg2−AaTnPio2n−s ainniboontsh itnheboetxhtratcheelluelxatrraacnedllular and iinnttrraacceelllluulalarr ccoommppaartrmtmenetns.ts.BasBeadsedononthethetytpyipcailcalexetrxatcrealcluellalur laarndandintirnatcreallcuellalrulaMrgMATgPA2−TP2− concecnotnrcaetniotrnastio((nMs g((AMTgPA2T−P)2o−)ao nadnd(M(MgAgATTPP2−2−))i,i, rreessppeecctitvievleyl)y, )t,hteheeqeuqiulibilriiburmiumpotpeontteianltioafl MofgMATgPA2−TP2− (mEoMdguAm(lETaPoMtd2goA−urTl)P1a2−t;w)oVrawR1s;aAcVsCaRlc,cAavulCcolua,lulvtaeomtdelude.m-.rCeeC-gxrxue,,glcacuootleanndtnneedeaxxnaiininno;i;onPnPcAAchNhaNanXnXn1n,1ee,llp;;paMMnaAnAneCnCxe,i,nmxmian1ax;xi1-iCa;-naACinoLAinoHLncMhHca1hMn, anc1nea,lnl.cecialu.lmciuhmomheoomstaesoisstasis. Another channel, the P2X7 receptor which is a trimeric ATP-gated cation channel, is known to progressively generate a large membrane pore that allow passage of molecules
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