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Mechanisms regulating the chamber‐specific structure of cardiac ATP‐sensitive potassium (KATP) channels
Author(s) -
Flagg Thomas P
Publication year - 2011
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.25.1_supplement.177.8
Subject(s) - sulfonylurea receptor , atp sensitive potassium channel , potassium channel , ventricle , protein subunit , gene isoform , kir6.2 , chemistry , medicine , endocrinology , microbiology and biotechnology , biology , biochemistry , gene , glibenclamide , diabetes mellitus
KATP channels are widely expressed in cardiac myocytes where they act as key sensors of cell metabolism during metabolic stress. All KATP channels share the same architecture—a K+ channel pore (Kir6.1 or Kir6.2) combines with a sulfonylurea receptor (SUR1, SUR2A or SUR2B) to form a functional channel. We discovered that cardiac KATP structure is chamber‐specific. Atrial KATP is made up of SUR1 and Kir6.2 while ventricular KATP contains SUR2A and Kir6.2. Quantitative RT‐PCR data demonstrate that SUR1 subunit mRNA expression is greater in mouse atrium compared with ventricle, while SUR2 mRNA is greater in the ventricle. This observation suggests that the chamber‐specific KATP composition is transcriptionally controlled. We have now identified two factors that regulate the expression of SURx subunits. Treatment of HL‐1 cells with the HDAC inhibitor, trichostatin A, causes a decrease in SUR1 mRNA with a concomitant increase in SUR2 mRNA. Similarly, treatment with glycolytic inhibitor, 2‐deoxyglucose, causes a coordinated decrease in SUR1 and increase in SUR2 expression. Taken together, the data show that the distribution of SURx transcripts correlates with chamber‐specific KATP channel structure. Moreover, we have identified two factors that modulate SURx subunit expression and present data suggesting that SUR1 and SUR2 expression is coordinated such that only one isoform is dominant.