Document Detail


pH-dependent modulation of connexin-based gap junctional uncouplers.
MedLine Citation:
PMID:  21606109     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gap junction (GJ) channels formed from connexin (Cx) proteins provide a direct pathway for electrical and metabolic cell–cell communication exhibiting high sensitivity to intracellular pH (pH(i)). We examined pH(i)-dependent modulation of junctional conductance (g(j)) of GJs formed of Cx26, mCx30.2, Cx36, Cx40, Cx43, Cx45, Cx46, Cx47 and Cx50 by reagents representing several distinct groups of uncouplers, such as long carbon chain alkanols (LCCAs), arachidonic acid, carbenoxolone, isoflurane, flufenamic acid and mefloquine. We demonstrate that alkalization by NH4Cl to pH ∼8 increased g(j) in cells expressing mCx30.2 and Cx45, yet did not affect g(j) of Cx26, Cx40, Cx46, Cx47 and Cx50 and decreased it in Cx43 and Cx36 GJs. Unexpectedly, cells expressing Cx45, but not other Cxs, exhibited full coupling recovery after alkalization with NH4Cl under the continuous presence of LCCAs, isoflurane and mefloquine. There was no coupling recovery by alkalization in the presence of arachidonic acid, carbenoxolone and flufenamic acid. In cells expressing Cx45, IC50 for octanol was 0.1, 0.25 and 2.68 mm at pH(i) values of 6.9, 7.2 and 8.1, respectively. Histidine modification of Cx45 protein by N-bromosuccinimide reduced the coupling-promoting effect of NH4Cl as well as the uncoupling effect of octanol. This suggests that LCCAs and some other uncouplers may act through the formation of hydrogen bonds with the as-of-yet unidentified histidine/s of the Cx45 GJ channel protein.
Authors:
Vytenis A Skeberdis; Lina Rimkute; Aiste Skeberdyte; Nerijus Paulauskas; Feliksas F Bukauskas
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-23
Journal Detail:
Title:  The Journal of physiology     Volume:  589     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-18     Completed Date:  2012-04-16     Revised Date:  2012-05-01    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  3495-506     Citation Subset:  IM    
Affiliation:
Lithuanian University of Health Sciences, Institute of Cardiology, 17 Sukilėliųu Avenue, Kaunas 50009, Lithuania.
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MeSH Terms
Descriptor/Qualifier:
Bromosuccinimide / pharmacology
Cell Communication / physiology*
Cells, Cultured
Connexins / antagonists & inhibitors,  chemistry,  metabolism*
Gap Junctions / metabolism*
HeLa Cells
Humans
Hydrogen Bonding
Hydrogen-Ion Concentration
Octanols / pharmacology
Protein Isoforms / metabolism
Grant Support
ID/Acronym/Agency:
HL084464/HL/NHLBI NIH HHS; NS072238/NS/NINDS NIH HHS; R01 HL084464/HL/NHLBI NIH HHS; R01 HL084464-04/HL/NHLBI NIH HHS; R01 NS072238/NS/NINDS NIH HHS; R01 NS072238-01/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Connexins; 0/Octanols; 0/Protein Isoforms; 39660-53-2/Bromosuccinimide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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