2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32.

2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32. Research Abstract Details 

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2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32. Abstract Text:

Liang Tao,Andrew L Harris,

2-aminoethoxydiphenyl borate (2-APB), a commonly used blocker of IP3-induced calcium ion release and of store-operated channels, inhibits gap junction conductance when applied to cultured cells. The character and pharmacology of this inhibition was explored using 1) hemichannels composed of connexin32 (Cx32) and/or connexin26 (Cx26) purified from native sources and from transfected HeLa cells in which the connexin had a cleavable C-terminal epitope tag and 2) the corresponding junctional channels. Using reconstituted hemichannels in a liposome-based transport-specific fractionation assay (TSF), 2-APB reversibly inhibited homomeric Cx32 and heteromeric Cx26/Cx32 channels from native tissue and their tagged forms from HeLa cells. The IC50-TSF value of the inhibition was approximately 47 microM at pH 6.5. 2-APB did not inhibit tagged homomeric Cx26 channels even after tag cleavage (leaving several amino acids at the carboxyl terminus). Protonated 2-APB is the inhibitory agent, but channel sensitivity to 2-APB also increases as pH is lowered. To help define the chemical requirements for inhibition, the effects of four structural analogs of 2-APB were determined. The inhibitory action of 2-APB was shown to be distinct from that of aminosulfonates. 2-APB and its analogs, except phenytoin, inhibited dye-coupling through junctional channels formed by all the tagged channel forms except Cx26, consistent with the TSF studies. However 2-APB significantly inhibited dye coupling between cells expressing untagged Cx26, suggesting that an unmodified C terminus is required for action on Cx26 channels. These results show that protonated 2-APB directly and reversibly inhibits connexin channels composed of Cx26 and/or Cx32 and suggest involvement of the carboxyl-terminal domain.

2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32. Publishing Authors By Initials

L Tao,AL Harris,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular pharmacology

VOLUME: 71

Page Numbers: 570-9

Journal Abbreviation: Mol. Pharmacol.

ISSN: 0026-895X

DAY: 9

MONTH: 11

YEAR: 2006

2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32. Information

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LANGUAGE: eng

NlmUniqueID: 35623

2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: antagonists & inhibitors

Chemical & Substance for Abstract: 2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32. Information

Substance Name: connexin 26

Registry Number: 127120-53-0

Grant and Affiliation Information for 2-aminoethoxydiphenyl borate directly inhibits channels composed of connexin26 and/or connexin32.

AFFILIATION: Department of Pharmacology, Zhongsan College of Medicine, Sun Yet-San University, Guangzhou China 510080. taol@mail.sysu.edu.cn

Country: United States

AGENCY: United States NIGMS

GRANT: GM61406

ACRONYM: GM

MEDLINETA: Mol Pharmacol

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