Glyceraldehyde 3-phosphate dehydrogenase serves as an accessory protein of the cardiac sarcolemmal KATP channel

S Jovanovic, Q Du, Russell Mckenzie Crawford, GR Budas, I Stagljar, A Jovanovic

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Cardiac sarcolemmal ATP-sensitive K+ (K-ATP) channels, composed of Kir6.2 and SUR2A subunits, are regulated by intracellular ATP and they couple the metabolic status of the cell with the membrane excitability. On the basis of previous studies, we have suggested that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) may be a part of the sarcolemmal K-ATP-channel protein complex. A polypeptide of similar to 42 kDa was immunoprecipitated with an anti-SUR2A antibody from guinea-pig cardiac membrane fraction and identified as GAPDH. Immunoprecipitation/western blotting analysis with anti-Kir6.2, anti-SUR2A and anti-GAPDH antibodies showed that GAPDH is a part of the sarcolemmal K-ATP-channel protein complex in vivo. Further studies with immunoprecipitation/western blotting and the membrane yeast two-hybrid system showed that GAPDH associates physically with the Kir6.2 but not the SUR2A subunit. Patch-clamp electrophysiology showed that GAPDH regulates K-ATP-channel activity irrespective of high intracellular ATP, by producing 1,3-bisphosphoglycerate, a K-ATP-channel opener. These results suggest that GAPDH is an integral part of the sarcolemmal K-ATP-channel protein complex, where it couples glycolysis with the K-ATP-channel activity.

Original languageEnglish
Pages (from-to)848 - 852
Number of pages5
JournalEMBO Journal
Volume6
Issue number9
DOIs
Publication statusPublished - Sept 2005

Keywords

  • heart
  • K-ATP channels
  • glyceraldehyde 3-phosphate dehydrogenase
  • SUR2A
  • Kir6.2
  • SPLIT-UBIQUITIN
  • IN-VIVO
  • SUBUNIT
  • SYSTEM
  • KINASE

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