Heart mitochondria contain functional ATP-dependent K+ channels

Zsombor Lacza, James A. Snipes, Allison W. Miller, Csaba Szabo, Gary Grover, David W. Busija

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Abstract

Recent observations challenged the functional importance or even the existence of mitochondrial ATP-dependent K+ (mitoKATP) channels. In the present study, we determined the presence of K ATP-channel subunits in mouse heart mitochondria, and investigated whether known openers or blockers of the channel can alter mitochondrial membrane potential. Investigation of the channel composition was performed with antibodies against KATP-channel subunits, namely the sulfonylurea receptor (SUR1 or SUR2) and the inwardly rectifying K+ channel (Kir6.1 or Kir6.2). Specific Kir6.1 and Kir6.2 proteins were found in the mitochondria by western blotting and immunogold electron microscopy. Neither SUR1 nor SUR2 was present in the mitochondria. In contrast, a mitochondrially enriched low molecular weight SUR2-like band was found at ∼25 kDa. Mitochondrial-transport tags were identified in the sequences of Kir6.1 and Kir6.2, but not in SUR1 or SUR2. The fluorescent BODIPY-glibenclamide labeling of mitochondria indicated direct sulfonylurea binding. Pharmacological characterization of mitoKATP was performed in isolated respiring heart mitochondria. Fluorescent confocal imaging with the membrane potential-sensitive dye MitoFluorRed showed that glibenclamide application changed membrane potential, while the specific mitoKATP-channel openers, diazoxide or BMS-191095, reversed the effect. Mitochondrially formed peroxynitrite is a physiological opener of the channel. We conclude that a functional KATP channel is present in heart mitochondria, which can be opened by diazoxide or BMS-191095. The channel can be composed of Kir6.1 and Kir6.2 subunits and does not contain either SUR1 or SUR2.

Original languageEnglish (US)
Pages (from-to)1339-1347
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume35
Issue number11
DOIs
StatePublished - Nov 2003
Externally publishedYes

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Keywords

  • ATP-dependent K channel
  • Diazoxide
  • FP15
  • Glibenclamide
  • Ischemic preconditioning
  • Sulfonylurea receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Lacza, Z., Snipes, J. A., Miller, A. W., Szabo, C., Grover, G., & Busija, D. W. (2003). Heart mitochondria contain functional ATP-dependent K+ channels. Journal of Molecular and Cellular Cardiology, 35(11), 1339-1347. https://doi.org/10.1016/S0022-2828(03)00249-9