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Interactions between A 2A adenosine receptor, hydrogen peroxide, and K ATP channel in coronary reactive hyperemia
Author(s) -
Sanjani Maryam Sharifi,
Asano Shinichi,
Dick Gregory,
Teng Bunyen,
Tilley Stephen,
Ledent Catherine,
Mustafa S Jamal
Publication year - 2012
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.26.1_supplement.863.6
Subject(s) - glibenclamide , chemistry , adenosine , hydrogen peroxide , patch clamp , receptor , adenosine receptor , potassium channel , biophysics , reactive hyperemia , medicine , endocrinology , biochemistry , agonist , blood flow , biology , diabetes mellitus
Myocardial metabolites such as adenosine mediate reactive hyperemia (RH) partially through glibenclamide‐sensitive K ATP channels in coronary vascular smooth muscle (VSM). We tested the hypothesis that A 2A receptors link to K ATP channel activation via hydrogen peroxide (H 2 O 2 ). Using A 2A knockout (KO), A 2B KO, and A 2A/2B double KO mice, we performed RH experiments in Langendorff‐perfused hearts and whole‐cell patch clamp experiments on isolated VSM cells. Flow repayment (ml/g) following a 15 sec occlusion in WT hearts was 6.3 ± 0.4 and reduced in A 2A KO (4.5 ± 0.2), but not A 2B KO (6.1 ± 0.3), mice. Catalase (1250 U/ml), which breaks down H 2 O 2 , significantly reduced flow repayment (ml/g) in WT (4.4 ± 0.4) but not A 2A KO (4.1 ± 0.4) hearts. Patch clamp experiments demonstrated that adenosine (10 μM) activated a glibenclamide (10 μM)‐sensitive conductance (nS/pF) in VSM cells from WT (0.05 ± 0.01) but not A 2A /A 2B KO (0.02 ± 0.01) mice. Additionally, in WT VSM cells, H 2 O 2 (1 mM) activated a glibenclamide‐sensitive conductance (0.07 ± 0.02 nS/pF). Our data indicate that A 2A receptors are coupled to K ATP channels, in part, via the production of H 2 O 2 as a signaling intermediate. HL027339 , HL094447 , HL071802 , T32 HL090610.