Source:http://linkedlifedata.com/resource/pubmed/id/11547349
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2001-9-7
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pubmed:abstractText |
Previous squid-axon studies identified a novel K/HCO3 cotransporter that is insensitive to disulfonic stilbene derivatives. This cotransporter presumably responds to intracellular alkali loads by moving K(+) and HCO(3)(-) out of the cell, tending to lower intracellular pH (pH(i)). With an inwardly directed K/HCO(3) gradient, the cotransporter mediates a net uptake of alkali (i.e., K(+) and HCO(3)(-) influx). Here we test the hypothesis that intracellular quaternary ammonium ions (QA(+)) inhibit the inwardly directed cotransporter by interacting at the intracellular K(+) site. We computed the equivalent HCO(3)(-) influx (J(HCO3)) mediated by the cotransporter from the rate of pH(i) increase, as measured with pH-sensitive microelectrodes. We dialyzed axons to pH(i) 8.0, using a dialysis fluid (DF) free of K(+), Na(+) and Cl(-). Our standard artificial seawater (ASW) also lacked Na(+), K(+) and Cl(-). After halting dialysis, we introduced an ASW containing 437 mm K(+) and 0.5% CO(2)/12 mm HCO(3)(-), which (i) caused membrane potential to become transiently very positive, and (ii) caused a rapid pHi decrease, due to CO(2) influx, followed by a slower plateau-phase pH(i) increase, due to inward cotransport of K(+) and HCO(3)(-). With no QA(+) in the DF, J(HCO3) was approximately 58 pmole cm(-2) sec(-1). With 400 mm tetraethylammonium (TEA(+)) in the DF, J(HCO3) was virtually zero. The apparent K(i) for intracellular TEA(+) was approximately 78 mm, more than two orders of magnitude greater than that obtained by others for inhibition of K(+) channels. Introducing 100 mm inhibitor into the DF reduced J(HCO3) to approximately 20 pmole cm(-2) sec(-1) for tetramethylammonium (TMA(+)), approximately 24 for TEA(+), approximately 10 for tetrapropylammonium (TPA(+)), and virtually zero for tetrabutylammonium (TBA(+)). The apparent K(i) value for TBA(+) is approximately 0.86 mm. The most potent inhibitor was phenyl-propyltetraethylammonium (PPTEA(+)), with an apparent K(i) of approximately 91 microm. Thus, trans-side quaternary ammonium ions inhibit K/HCO(3) influx in the potency sequence PPTEA(+) > TBA(+) > TPA(+) > TEA(+) congruent with TMA(+). The identification of inhibitors of the K/HCO(3) cotransporter, for which no inhibitors previously existed, will facilitate the study of this transporter.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bicarbonates,
http://linkedlifedata.com/resource/pubmed/chemical/Ganglionic Stimulants,
http://linkedlifedata.com/resource/pubmed/chemical/Ions,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Quaternary Ammonium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Bicarbonate Symporters,
http://linkedlifedata.com/resource/pubmed/chemical/Tetraethylammonium,
http://linkedlifedata.com/resource/pubmed/chemical/tetrabutylammonium,
http://linkedlifedata.com/resource/pubmed/chemical/tetramethylammonium,
http://linkedlifedata.com/resource/pubmed/chemical/tetrapropylammonium
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-2631
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
183
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25-32
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11547349-Animals,
pubmed-meshheading:11547349-Axons,
pubmed-meshheading:11547349-Bicarbonates,
pubmed-meshheading:11547349-Decapodiformes,
pubmed-meshheading:11547349-Dose-Response Relationship, Drug,
pubmed-meshheading:11547349-Ganglionic Stimulants,
pubmed-meshheading:11547349-Ions,
pubmed-meshheading:11547349-Potassium,
pubmed-meshheading:11547349-Potassium Channel Blockers,
pubmed-meshheading:11547349-Quaternary Ammonium Compounds,
pubmed-meshheading:11547349-Sodium-Bicarbonate Symporters,
pubmed-meshheading:11547349-Tetraethylammonium
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pubmed:year |
2001
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pubmed:articleTitle |
Inhibition of K/HCO(3) cotransport in squid axons by quaternary ammonium ions.
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pubmed:affiliation |
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA. bruce.davis@yale.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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