In vivo airway surface liquid Cl- analysis with solid-state electrodes
The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl-] is p...
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description | The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl-] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl-] in the "thin" ASL (approximately 30 microm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl-] in vivo. In initial experiments, the electrode measured [Cl-] in physiologic salt solutions, small volume (7.6 microl) test solutions, and in in vitro cell culture models, with > or =93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl- measurements were made in the following airway regions and species. First, ASL [Cl-] was measured in normal human nasal cavity and averaged 117.3 +/- 11.2 mM (n = 6). Second, ASL [Cl-] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 +/- 1.8 mM; (n = 6) and 126.9 +/- 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 +/- 4.2 mM (n = 13); and monkey bronchus = 112.3 +/- 10.9 mM (n = 3). Third, Cl- measurements were made in small (1-2 mm) diameter airways of the rabbit (108.3 +/- 7.1 mM, n = 5) and monkey (128.5 +/- 6.8 mM, n = 3). The measured [Cl-], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology. |
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Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl-] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl-] in the "thin" ASL (approximately 30 microm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl-] in vivo. In initial experiments, the electrode measured [Cl-] in physiologic salt solutions, small volume (7.6 microl) test solutions, and in in vitro cell culture models, with > or =93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl- measurements were made in the following airway regions and species. First, ASL [Cl-] was measured in normal human nasal cavity and averaged 117.3 +/- 11.2 mM (n = 6). Second, ASL [Cl-] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 +/- 1.8 mM; (n = 6) and 126.9 +/- 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 +/- 4.2 mM (n = 13); and monkey bronchus = 112.3 +/- 10.9 mM (n = 3). Third, Cl- measurements were made in small (1-2 mm) diameter airways of the rabbit (108.3 +/- 7.1 mM, n = 5) and monkey (128.5 +/- 6.8 mM, n = 3). The measured [Cl-], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology.</description><identifier>ISSN: 0022-1295</identifier><identifier>EISSN: 1540-7748</identifier><identifier>DOI: 10.1085/jgp.119.1.3</identifier><identifier>PMID: 11773234</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Adult ; Animals ; Bronchi - chemistry ; Bronchi - physiology ; Chlorides - analysis ; Chlorides - standards ; Female ; Humans ; Ion-Selective Electrodes - standards ; Macaca mulatta ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Nasal Cavity - chemistry ; Nasal Cavity - physiology ; Original ; Rabbits ; Solutions ; Trachea - chemistry ; Trachea - physiology</subject><ispartof>The Journal of general physiology, 2002-01, Vol.119 (1), p.3-14</ispartof><rights>2002 The Rockefeller University Press 2002 The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-ff4846c908fce3d5643e5ff7e967c4ee886ef6ee532e230af59c8aaad00bfd533</citedby><cites>FETCH-LOGICAL-c377t-ff4846c908fce3d5643e5ff7e967c4ee886ef6ee532e230af59c8aaad00bfd533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2233861/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2233861/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,887,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11773234$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Caldwell, Ray A</creatorcontrib><creatorcontrib>Grubb, Barbara R</creatorcontrib><creatorcontrib>Tarran, Robert</creatorcontrib><creatorcontrib>Boucher, Richard C</creatorcontrib><creatorcontrib>Knowles, Michael R</creatorcontrib><creatorcontrib>Barker, Pierre M</creatorcontrib><title>In vivo airway surface liquid Cl- analysis with solid-state electrodes</title><title>The Journal of general physiology</title><addtitle>J Gen Physiol</addtitle><description>The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl-] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl-] in the "thin" ASL (approximately 30 microm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl-] in vivo. In initial experiments, the electrode measured [Cl-] in physiologic salt solutions, small volume (7.6 microl) test solutions, and in in vitro cell culture models, with > or =93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl- measurements were made in the following airway regions and species. First, ASL [Cl-] was measured in normal human nasal cavity and averaged 117.3 +/- 11.2 mM (n = 6). Second, ASL [Cl-] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 +/- 1.8 mM; (n = 6) and 126.9 +/- 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 +/- 4.2 mM (n = 13); and monkey bronchus = 112.3 +/- 10.9 mM (n = 3). Third, Cl- measurements were made in small (1-2 mm) diameter airways of the rabbit (108.3 +/- 7.1 mM, n = 5) and monkey (128.5 +/- 6.8 mM, n = 3). The measured [Cl-], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology.</description><subject>Adult</subject><subject>Animals</subject><subject>Bronchi - chemistry</subject><subject>Bronchi - physiology</subject><subject>Chlorides - analysis</subject><subject>Chlorides - standards</subject><subject>Female</subject><subject>Humans</subject><subject>Ion-Selective Electrodes - standards</subject><subject>Macaca mulatta</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>Nasal Cavity - chemistry</subject><subject>Nasal Cavity - physiology</subject><subject>Original</subject><subject>Rabbits</subject><subject>Solutions</subject><subject>Trachea - chemistry</subject><subject>Trachea - physiology</subject><issn>0022-1295</issn><issn>1540-7748</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkD1PwzAQhi0EoqUwsSNPLCjBH3GcLEioolCpEgvMluucW1duUuykVf89qVrxccsN9-i9Vw9Ct5SklBTicbXYpJSWKU35GRpSkZFEyqw4R0NCGEsoK8UAXcW4Iv0IRi7RgFIpOePZEE2mNd66bYO1Czu9x7ELVhvA3n11rsJjn2Bda7-PLuKda5c4Nt5VSWx1Cxg8mDY0FcRrdGG1j3Bz2iP0OXn5GL8ls_fX6fh5lhguZZtYmxVZbkpSWAO8EnnGQVgrocylyQCKIgebAwjOgHGirShNobWuCJnbSnA-Qk_H3E03X0NloG6D9moT3FqHvWq0U_8vtVuqRbNVjHFe5LQPuD8FhOarg9iqtYsGvNc1NF1UknKRUyF68OEImtDEGMD-PKFEHbyr3rvqvSuqDr3u_vb6ZU-i-TdWmICS</recordid><startdate>200201</startdate><enddate>200201</enddate><creator>Caldwell, Ray A</creator><creator>Grubb, Barbara R</creator><creator>Tarran, Robert</creator><creator>Boucher, Richard C</creator><creator>Knowles, Michael R</creator><creator>Barker, Pierre M</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200201</creationdate><title>In vivo airway surface liquid Cl- analysis with solid-state electrodes</title><author>Caldwell, Ray A ; Grubb, Barbara R ; Tarran, Robert ; Boucher, Richard C ; Knowles, Michael R ; Barker, Pierre M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-ff4846c908fce3d5643e5ff7e967c4ee886ef6ee532e230af59c8aaad00bfd533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Bronchi - chemistry</topic><topic>Bronchi - physiology</topic><topic>Chlorides - analysis</topic><topic>Chlorides - standards</topic><topic>Female</topic><topic>Humans</topic><topic>Ion-Selective Electrodes - standards</topic><topic>Macaca mulatta</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>Nasal Cavity - chemistry</topic><topic>Nasal Cavity - physiology</topic><topic>Original</topic><topic>Rabbits</topic><topic>Solutions</topic><topic>Trachea - chemistry</topic><topic>Trachea - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Caldwell, Ray A</creatorcontrib><creatorcontrib>Grubb, Barbara R</creatorcontrib><creatorcontrib>Tarran, Robert</creatorcontrib><creatorcontrib>Boucher, Richard C</creatorcontrib><creatorcontrib>Knowles, Michael R</creatorcontrib><creatorcontrib>Barker, Pierre M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of general physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caldwell, Ray A</au><au>Grubb, Barbara R</au><au>Tarran, Robert</au><au>Boucher, Richard C</au><au>Knowles, Michael R</au><au>Barker, Pierre M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo airway surface liquid Cl- analysis with solid-state electrodes</atitle><jtitle>The Journal of general physiology</jtitle><addtitle>J Gen Physiol</addtitle><date>2002-01</date><risdate>2002</risdate><volume>119</volume><issue>1</issue><spage>3</spage><epage>14</epage><pages>3-14</pages><issn>0022-1295</issn><eissn>1540-7748</eissn><abstract>The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl-] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl-] in the "thin" ASL (approximately 30 microm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl-] in vivo. In initial experiments, the electrode measured [Cl-] in physiologic salt solutions, small volume (7.6 microl) test solutions, and in in vitro cell culture models, with > or =93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl- measurements were made in the following airway regions and species. First, ASL [Cl-] was measured in normal human nasal cavity and averaged 117.3 +/- 11.2 mM (n = 6). Second, ASL [Cl-] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 +/- 1.8 mM; (n = 6) and 126.9 +/- 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 +/- 4.2 mM (n = 13); and monkey bronchus = 112.3 +/- 10.9 mM (n = 3). Third, Cl- measurements were made in small (1-2 mm) diameter airways of the rabbit (108.3 +/- 7.1 mM, n = 5) and monkey (128.5 +/- 6.8 mM, n = 3). The measured [Cl-], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>11773234</pmid><doi>10.1085/jgp.119.1.3</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Animals Bronchi - chemistry Bronchi - physiology Chlorides - analysis Chlorides - standards Female Humans Ion-Selective Electrodes - standards Macaca mulatta Male Mice Mice, Inbred C57BL Middle Aged Nasal Cavity - chemistry Nasal Cavity - physiology Original Rabbits Solutions Trachea - chemistry Trachea - physiology |
title | In vivo airway surface liquid Cl- analysis with solid-state electrodes |
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