© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Mitochondria are the main ATP source for a cytosolic pool controlling the activity of ATP-sensitive K+ channels in mouse cardiac myocytes
Institut für Physiologie, Abt. Herz-Kreislauf-Physiologie, Friedrich-Schiller-Universität Jena, D-07740 Jena, Germany
* Corresponding author. Tel.: +49-3641-934-351; fax: +49-3641-933-202 kben{at}mti-n.uni-jena.de
Objective: The aim was to identify the major ATP source controlling the activity of sarcolemmal KATP channels in ventricular cardiomyocytes. Methods: KATP-channel current (IKATP) was measured with the patch-clamp technique in either the whole-cell (glycogenolysis blocked by 10 mmol/l EGTA), cell-attached, or inside-out configuration. Results: In the absence of any substrate, IKATP (amplitude 31±4 nA; n=5) appeared spontaneously 520±160 s (n=6) after whole-cell access. This latency was shortened by exposure to anoxia (117±33 s, n=32) and even more by uncoupling (1–10 µmol/l FCCP; 25±3 s; n=13) while the amplitude was unchanged. During metabolic inhibition the latency was remarkably prolonged when the F1F0-ATPase was blocked by oligomycin, suggesting that under those conditions the F1F0-ATPase is the major ATP consumer. Glucose (5.5–20.0 mmol/l) in the bath solution did not affect the amplitude of IKATP but prolonged its latency compared to respective substrate-free conditions. However, IKATP was blocked immediately by mitochondrial substrates. FCCP also induced large IKATP in cell-attached measurements in either the absence or presence of glucose and oligomycin. Conclusions: The activity of KATP channels in cardiomyocytes of mice is controlled by a cytosolic [ATP] pool for which oxidative phosphorylation is the predominant ATP source.
KEYWORDS Energy metabolism; Glycolysis; Hypoxia/anoxia; K-ATP channel; Mitochondria; Oxidative phosphorylation
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