Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells
Acidification of the resorption pits, which is essential for dissolving bone, is produced by secretion of protons through vacuolar H + -ATPases in the plasma membrane of bone-resorbing cells, osteoclasts. Consequently, osteoclasts face highly acidic extracellular environments, where the pH gradient...
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| Veröffentlicht in: | Pflügers Archiv 2016-05, Vol.468 (5), p.837-847 |
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| creator | Kuno, Miyuki Li, Guangshuai Moriura, Yoshie Hino, Yoshiko Kawawaki, Junko Sakai, Hiromu |
| description | Acidification of the resorption pits, which is essential for dissolving bone, is produced by secretion of protons through vacuolar H
+
-ATPases in the plasma membrane of bone-resorbing cells, osteoclasts. Consequently, osteoclasts face highly acidic extracellular environments, where the pH gradient across the plasma membrane could generate a force driving protons into the cells. Proton influx mechanisms during the acid exposure are largely unknown, however. In this study, we investigated extracellular-acid-inducible proton influx currents in osteoclast-like cells derived from a macrophage cell line (RAW264). Decreasing extracellular pH to |
| doi_str_mv | 10.1007/s00424-016-1796-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1805498122</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4032850591</sourcerecordid><originalsourceid>FETCH-LOGICAL-p245t-7261f4ee2b167dd412d69431ad731be8534a7b0c2944d18e18aa66f096cab0bf3</originalsourceid><addsrcrecordid>eNqFkU1LxDAQhoMouq7-AC9S8OIlOpNkk_Qoi1-w4EVvQkjbVLP2Y01a0H9vyiqIF0-Z8D7MvDMvIScIFwigLiOAYIICSooql1TtkBkKzigD5LtkBsCRSiX1ATmMcQ0ATGi2Tw6Y1IJDzmfk-ar0FfVdNZa-aFy2Cf3Qd5nv6mb8yMoxBNcNMf2z4TWpjY2tzVrXFsF2LuvrrB2Dn6o4uL5M8kAb_-ay0jVNPCJ7tW2iO_5-5-Tp5vpxeUdXD7f3y6sV3TCxGKhiEmvhHCtQqqoSyCqZC462UhwLpxdcWFVAyXIhKtQOtbVS1pDL0hZQ1HxOzrd9k_v30cXBtD5ODpLHfowGNSxErpGx_1GlhZCYTprQsz_ouh9DlxaZKK64BMkTdfpNjUXrKrMJvrXh0_ycOAFsC8QkdS8u_GoDZsrRbHM0aaiZcjSKfwFE2IzR</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1783736063</pqid></control><display><type>article</type><title>Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Kuno, Miyuki ; Li, Guangshuai ; Moriura, Yoshie ; Hino, Yoshiko ; Kawawaki, Junko ; Sakai, Hiromu</creator><creatorcontrib>Kuno, Miyuki ; Li, Guangshuai ; Moriura, Yoshie ; Hino, Yoshiko ; Kawawaki, Junko ; Sakai, Hiromu</creatorcontrib><description>Acidification of the resorption pits, which is essential for dissolving bone, is produced by secretion of protons through vacuolar H
+
-ATPases in the plasma membrane of bone-resorbing cells, osteoclasts. Consequently, osteoclasts face highly acidic extracellular environments, where the pH gradient across the plasma membrane could generate a force driving protons into the cells. Proton influx mechanisms during the acid exposure are largely unknown, however. In this study, we investigated extracellular-acid-inducible proton influx currents in osteoclast-like cells derived from a macrophage cell line (RAW264). Decreasing extracellular pH to <5.5 induced non-ohmic inward currents. The reversal potentials depended on the pH gradients across the membrane and were independent of concentrations of Na
+
, Cl
−
, and HCO
3
−
, suggesting that they were carried largely by protons. The acid-inducible proton influx currents were not inhibited by amiloride, a widely used blocker for cation channels/transporters, or by 4,4'-diisothiocyanato-2,2'-stilbenesulfonate(DIDS) which blocks anion channels/transporters. Additionally, the currents were not significantly affected by V-ATPase inhibitors, bafilomycin A
1
and N,N’-dicyclohexylcarbodiimide. Extracellular Ca
2+
(10 mM) did not affect the currents, but 1 mM ZnCl
2
decreased the currents partially. The intracellular pH in the vicinity of the plasma membrane was dropped by the acid-inducible H
+
influx currents, which caused overshoot of the voltage-gated H
+
channels after removal of acids. The H
+
influx currents were smaller in undifferentiated, mononuclear RAW cells and were negligible in COS7 cells. These data suggest that the acid-inducible H
+
influx (H
+
leak) pathway may be an additional mechanism modifying the pH environments of osteoclasts upon exposure to strong acids.</description><identifier>ISSN: 0031-6768</identifier><identifier>EISSN: 1432-2013</identifier><identifier>DOI: 10.1007/s00424-016-1796-7</identifier><identifier>PMID: 26843093</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology ; Action Potentials ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Calcium - pharmacology ; Cell Biology ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cercopithecus aethiops ; Chlorides - pharmacology ; COS Cells ; Human Physiology ; Hydrogen-Ion Concentration ; Ion Channels ; Ion Channels - drug effects ; Ion Channels - metabolism ; Mice ; Molecular Medicine ; Neurosciences ; Osteoclasts - metabolism ; Protons ; Receptors ; Receptors and Transporters ; Zinc Compounds - pharmacology</subject><ispartof>Pflügers Archiv, 2016-05, Vol.468 (5), p.837-847</ispartof><rights>Springer-Verlag Berlin Heidelberg 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-p245t-7261f4ee2b167dd412d69431ad731be8534a7b0c2944d18e18aa66f096cab0bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00424-016-1796-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00424-016-1796-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26843093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuno, Miyuki</creatorcontrib><creatorcontrib>Li, Guangshuai</creatorcontrib><creatorcontrib>Moriura, Yoshie</creatorcontrib><creatorcontrib>Hino, Yoshiko</creatorcontrib><creatorcontrib>Kawawaki, Junko</creatorcontrib><creatorcontrib>Sakai, Hiromu</creatorcontrib><title>Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells</title><title>Pflügers Archiv</title><addtitle>Pflugers Arch - Eur J Physiol</addtitle><addtitle>Pflugers Arch</addtitle><description>Acidification of the resorption pits, which is essential for dissolving bone, is produced by secretion of protons through vacuolar H
+
-ATPases in the plasma membrane of bone-resorbing cells, osteoclasts. Consequently, osteoclasts face highly acidic extracellular environments, where the pH gradient across the plasma membrane could generate a force driving protons into the cells. Proton influx mechanisms during the acid exposure are largely unknown, however. In this study, we investigated extracellular-acid-inducible proton influx currents in osteoclast-like cells derived from a macrophage cell line (RAW264). Decreasing extracellular pH to <5.5 induced non-ohmic inward currents. The reversal potentials depended on the pH gradients across the membrane and were independent of concentrations of Na
+
, Cl
−
, and HCO
3
−
, suggesting that they were carried largely by protons. The acid-inducible proton influx currents were not inhibited by amiloride, a widely used blocker for cation channels/transporters, or by 4,4'-diisothiocyanato-2,2'-stilbenesulfonate(DIDS) which blocks anion channels/transporters. Additionally, the currents were not significantly affected by V-ATPase inhibitors, bafilomycin A
1
and N,N’-dicyclohexylcarbodiimide. Extracellular Ca
2+
(10 mM) did not affect the currents, but 1 mM ZnCl
2
decreased the currents partially. The intracellular pH in the vicinity of the plasma membrane was dropped by the acid-inducible H
+
influx currents, which caused overshoot of the voltage-gated H
+
channels after removal of acids. The H
+
influx currents were smaller in undifferentiated, mononuclear RAW cells and were negligible in COS7 cells. These data suggest that the acid-inducible H
+
influx (H
+
leak) pathway may be an additional mechanism modifying the pH environments of osteoclasts upon exposure to strong acids.</description><subject>4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology</subject><subject>Action Potentials</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Calcium - pharmacology</subject><subject>Cell Biology</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Cercopithecus aethiops</subject><subject>Chlorides - pharmacology</subject><subject>COS Cells</subject><subject>Human Physiology</subject><subject>Hydrogen-Ion Concentration</subject><subject>Ion Channels</subject><subject>Ion Channels - drug effects</subject><subject>Ion Channels - metabolism</subject><subject>Mice</subject><subject>Molecular Medicine</subject><subject>Neurosciences</subject><subject>Osteoclasts - metabolism</subject><subject>Protons</subject><subject>Receptors</subject><subject>Receptors and Transporters</subject><subject>Zinc Compounds - pharmacology</subject><issn>0031-6768</issn><issn>1432-2013</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkU1LxDAQhoMouq7-AC9S8OIlOpNkk_Qoi1-w4EVvQkjbVLP2Y01a0H9vyiqIF0-Z8D7MvDMvIScIFwigLiOAYIICSooql1TtkBkKzigD5LtkBsCRSiX1ATmMcQ0ATGi2Tw6Y1IJDzmfk-ar0FfVdNZa-aFy2Cf3Qd5nv6mb8yMoxBNcNMf2z4TWpjY2tzVrXFsF2LuvrrB2Dn6o4uL5M8kAb_-ay0jVNPCJ7tW2iO_5-5-Tp5vpxeUdXD7f3y6sV3TCxGKhiEmvhHCtQqqoSyCqZC462UhwLpxdcWFVAyXIhKtQOtbVS1pDL0hZQ1HxOzrd9k_v30cXBtD5ODpLHfowGNSxErpGx_1GlhZCYTprQsz_ouh9DlxaZKK64BMkTdfpNjUXrKrMJvrXh0_ycOAFsC8QkdS8u_GoDZsrRbHM0aaiZcjSKfwFE2IzR</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Kuno, Miyuki</creator><creator>Li, Guangshuai</creator><creator>Moriura, Yoshie</creator><creator>Hino, Yoshiko</creator><creator>Kawawaki, Junko</creator><creator>Sakai, Hiromu</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20160501</creationdate><title>Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells</title><author>Kuno, Miyuki ; Li, Guangshuai ; Moriura, Yoshie ; Hino, Yoshiko ; Kawawaki, Junko ; Sakai, Hiromu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p245t-7261f4ee2b167dd412d69431ad731be8534a7b0c2944d18e18aa66f096cab0bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology</topic><topic>Action Potentials</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Calcium - pharmacology</topic><topic>Cell Biology</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cercopithecus aethiops</topic><topic>Chlorides - pharmacology</topic><topic>COS Cells</topic><topic>Human Physiology</topic><topic>Hydrogen-Ion Concentration</topic><topic>Ion Channels</topic><topic>Ion Channels - drug effects</topic><topic>Ion Channels - metabolism</topic><topic>Mice</topic><topic>Molecular Medicine</topic><topic>Neurosciences</topic><topic>Osteoclasts - metabolism</topic><topic>Protons</topic><topic>Receptors</topic><topic>Receptors and Transporters</topic><topic>Zinc Compounds - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuno, Miyuki</creatorcontrib><creatorcontrib>Li, Guangshuai</creatorcontrib><creatorcontrib>Moriura, Yoshie</creatorcontrib><creatorcontrib>Hino, Yoshiko</creatorcontrib><creatorcontrib>Kawawaki, Junko</creatorcontrib><creatorcontrib>Sakai, Hiromu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Pflügers Archiv</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuno, Miyuki</au><au>Li, Guangshuai</au><au>Moriura, Yoshie</au><au>Hino, Yoshiko</au><au>Kawawaki, Junko</au><au>Sakai, Hiromu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells</atitle><jtitle>Pflügers Archiv</jtitle><stitle>Pflugers Arch - Eur J Physiol</stitle><addtitle>Pflugers Arch</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>468</volume><issue>5</issue><spage>837</spage><epage>847</epage><pages>837-847</pages><issn>0031-6768</issn><eissn>1432-2013</eissn><abstract>Acidification of the resorption pits, which is essential for dissolving bone, is produced by secretion of protons through vacuolar H
+
-ATPases in the plasma membrane of bone-resorbing cells, osteoclasts. Consequently, osteoclasts face highly acidic extracellular environments, where the pH gradient across the plasma membrane could generate a force driving protons into the cells. Proton influx mechanisms during the acid exposure are largely unknown, however. In this study, we investigated extracellular-acid-inducible proton influx currents in osteoclast-like cells derived from a macrophage cell line (RAW264). Decreasing extracellular pH to <5.5 induced non-ohmic inward currents. The reversal potentials depended on the pH gradients across the membrane and were independent of concentrations of Na
+
, Cl
−
, and HCO
3
−
, suggesting that they were carried largely by protons. The acid-inducible proton influx currents were not inhibited by amiloride, a widely used blocker for cation channels/transporters, or by 4,4'-diisothiocyanato-2,2'-stilbenesulfonate(DIDS) which blocks anion channels/transporters. Additionally, the currents were not significantly affected by V-ATPase inhibitors, bafilomycin A
1
and N,N’-dicyclohexylcarbodiimide. Extracellular Ca
2+
(10 mM) did not affect the currents, but 1 mM ZnCl
2
decreased the currents partially. The intracellular pH in the vicinity of the plasma membrane was dropped by the acid-inducible H
+
influx currents, which caused overshoot of the voltage-gated H
+
channels after removal of acids. The H
+
influx currents were smaller in undifferentiated, mononuclear RAW cells and were negligible in COS7 cells. These data suggest that the acid-inducible H
+
influx (H
+
leak) pathway may be an additional mechanism modifying the pH environments of osteoclasts upon exposure to strong acids.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26843093</pmid><doi>10.1007/s00424-016-1796-7</doi><tpages>11</tpages></addata></record> |
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| identifier | ISSN: 0031-6768 |
| ispartof | Pflügers Archiv, 2016-05, Vol.468 (5), p.837-847 |
| issn | 0031-6768 1432-2013 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology Action Potentials Animals Biomedical and Life Sciences Biomedicine Calcium - pharmacology Cell Biology Cell Membrane - drug effects Cell Membrane - metabolism Cercopithecus aethiops Chlorides - pharmacology COS Cells Human Physiology Hydrogen-Ion Concentration Ion Channels Ion Channels - drug effects Ion Channels - metabolism Mice Molecular Medicine Neurosciences Osteoclasts - metabolism Protons Receptors Receptors and Transporters Zinc Compounds - pharmacology |
| title | Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells |
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