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(‐)‐Epigallocatechin‐3‐gallate uncouples ATP‐sensitive K + channels from phosphatidylinositol polyphosphates and ATP
Author(s) -
Song DaeKyu,
Jin JunYup,
Han Jin,
Lee Jin Ho,
Bae JaeHoon
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a957-d
Subject(s) - kir6.2 , chemistry , epigallocatechin gallate , potassium channel , atp sensitive potassium channel , sulfonylurea receptor , phosphatidylinositol , biochemistry , adenosine triphosphate , protein subunit , membrane potential , channel blocker , biophysics , glibenclamide , endocrinology , kinase , biology , calcium , polyphenol , diabetes mellitus , gene , antioxidant , organic chemistry
Of the green tea catechins, (‐)‐epigallocatechin‐3‐gallate (EGCG) and (‐)‐epicatechin‐3‐gallate (ECG), but not (‐)‐epicatechin and (‐)‐epigallocatechin, inhibit the activity of ATP‐sensitive potassium (K ATP ) channels. Using cloned K ATP channels, we show that only EGCG (1 μM), but not other epicatechins, significantly block channel refreshment after ATP wash‐out, suggesting that an interaction of phosphatidylinositol polyphosphates (PIPs) with the channel is impaired by EGCG. A ten fold higher concentration (10 μM) of EGCG reduced the channel sensitivity to ATP, but not AMP and ADP. This effect of EGCG was greater in the channel with the sulphonylurea receptor (SUR) than with the inwardly‐rectifying K + channel (Kir6.2) alone. Neomycin, a polycation, profoundly suppressed the effect of EGCG. Glucose‐stimulated cytosolic Ca 2+ elevation and insulin secretion in rat islet cells were impaired in the presence of concentrations higher than 5 μM EGCG. In rabbit cardiac myocytes, dinitrophenol‐induced opening of the channel was delayed by treatment with 1 μM EGCG. EGCG may preferentially interact with PIPs‐binding sites on the cytoplasmic termini of the Kir6.2 subunit. SUR1 further endows EGCG with the ability to interfere with an interaction of the γ‐phosphate tail of ATP with Kir6.2. The specificity of EGCG suggests that the 5′‐OH of the B‐ring on the pyrogallol moiety in the EGCG molecule may be critical for the effects of EGCG on the K ATP channel.