Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics

Richard J Gumina; Darko Pucar; Peter Bast; Denice M Hodgson; Christopher E Kurtz; Petras P Dzeja; Takashi Miki; Susumu Seino; Andre Terzic

doi:10.1152/ajpheart.00057.2003

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Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics

Journal article

Peer reviewed

Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics

Richard J Gumina, Darko Pucar, Peter Bast, Denice M Hodgson, Christopher E Kurtz, Petras P Dzeja, Takashi Miki, Susumu Seino and Andre Terzic

American journal of physiology. Heart and circulatory physiology, Vol.284(6), pp.H2106-2113

06/2003

DOI: 10.1152/ajpheart.00057.2003

PMID: 12598229

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Abstract

Although ischemic preconditioning induces bioenergetic tolerance and thereby remodels energy metabolism that is crucial for postischemic recovery of the heart, the molecular components associated with preservation of cellular energy production, transfer, and utilization are not fully understood. Here myocardial bioenergetic dynamics were assessed by (18)O-assisted (31)P-NMR spectroscopy in control or preconditioned hearts from wild-type (WT) or Kir6.2-knockout (Kir6.2-KO) mice that lack metabolism-sensing sarcolemmal ATP-sensitive K(+) (K(ATP)) channels. In WT vs. Kir6.2-KO hearts, preconditioning induced a significantly higher total ATP turnover (232 +/- 20 vs. 155 +/- 15 nmol x mg protein(-1) x min(-1)), ATP synthesis rate (58 +/- 3 vs. 46 +/- 3% (18)O labeling of gamma-ATP), and ATP consumption rate (51 +/- 4 vs. 31 +/- 4% (18)O labeling of P(i)) after ischemia-reperfusion. Moreover, preconditioning preserved cardiac creatine kinase-catalyzed phosphotransfer in WT (234 +/- 26 nmol x mg protein(-1) x min(-1)) but not Kir6.2-KO (133 +/- 18 nmol x mg protein(-1) x min(-1)) hearts. In contrast with WT hearts, preconditioning failed to preserve contractile recovery in Kir6.2-KO hearts, as tight coupling between postischemic performance and high-energy phosphoryl transfer was compromised in the K(ATP)-channel-deficient myocardium. Thus intact K(ATP) channels are integral in ischemic preconditioning-induced protection of cellular energetic dynamics and associated cardiac performance.

Magnetic Resonance Spectroscopy

Heart - physiology

Potassium Channels, Inwardly Rectifying - genetics

Mice, Knockout

Animals

Ischemic Preconditioning, Myocardial

Adenosine Triphosphate - metabolism

Myocardium - metabolism

Potassium Channels, Inwardly Rectifying - physiology

Myocardial Ischemia - physiopathology

Mice

Phosphocreatine - metabolism

Energy Metabolism - genetics

Energy Metabolism - physiology

In Vitro Techniques

Sarcolemma - metabolism

Details

Title: Subtitle: Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics
Creators: Richard J Gumina - Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905, USA
Darko Pucar
Peter Bast
Denice M Hodgson
Christopher E Kurtz
Petras P Dzeja
Takashi Miki
Susumu Seino
Andre Terzic
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.284(6), pp.H2106-2113
DOI: 10.1152/ajpheart.00057.2003
PMID: 12598229
ISSN: 0363-6135
eISSN: 1522-1539
Grant note: HL-64822 / NHLBI NIH HHS HL-07111 / NHLBI NIH HHS
Language: English
Date published: 06/2003
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984094676402771

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