The mitochondrial KATP channel as a receptor for potassium channel openers

Keith D. Garlid, Petr Paucek, Vladimir Yarov-Yarovoy, Xiaocheng Sun, Peter A. Schindler

Research output: Contribution to journalArticle

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Abstract

The biochemical properties of the mitochondrial KATP channel are very similar to those of plasma membrane KATP channels, including inhibition by low concentrations of ATP and glyburide (Paucek, P., Mironova, G., Mahdi, F., Beavis, A. D., Woldegiorgis, G., and Garlid, K. D. (1992) J. Biol. Chem. 267, 26062-26069). Plasma membrane KATP channels are highly sensitive to the family of drugs known as K+ channel openers, raising the question whether mitochondrial KATP channels are similarly sensitive to these agents. We addressed this question by measuring K+ flux in intact rat liver mitochondria and in liposomes containing KATP channels purified from rat liver and beef heart mitochondria. K+ channel openers completely reversed ATP inhibition of K+ flux in both systems. In liposomes, ATP-inhibited K+ flux was restored by diazoxide (K1/2 = 0.4 μM), cromakalim (K1/2 = 1 μM), and two developmental cromakalim analogues, EMD60480 and EMD57970 (K1/2 = 6 nM). Similar K1/2 values were observed in intact mitochondria. These potencies are well within the range observed with plasma membrane KATP channels. We also compared the potencies of these K+ channel openers on the plasma membrane KATP channel purified from beef heart myocytes. The KATP channel from cardiac mitochondria is 2000-fold more sensitive to diazoxide than the channel from cardiac sarcolemma, indicating that two distinct receptor subtypes coexist within the myocyte. We suggest that the mitochondrial KATP channel is an important intracellular receptor that should be taken into account in considering the pharmacology of K+ channel openers.

Original languageEnglish (US)
Pages (from-to)8796-8799
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number15
StatePublished - Apr 12 1996
Externally publishedYes

Fingerprint

KATP Channels
Potassium Channels
Mitochondria
Cell membranes
Ion Channels
Cell Membrane
Cromakalim
Diazoxide
Beef
Adenosine Triphosphate
Fluxes
Liposomes
Liver
Muscle Cells
Rats
Heart Mitochondria
Sarcolemma
Glyburide
Liver Mitochondrion
mitochondrial K(ATP) channel

ASJC Scopus subject areas

  • Biochemistry

Cite this

Garlid, K. D., Paucek, P., Yarov-Yarovoy, V., Sun, X., & Schindler, P. A. (1996). The mitochondrial KATP channel as a receptor for potassium channel openers. Journal of Biological Chemistry, 271(15), 8796-8799.

The mitochondrial KATP channel as a receptor for potassium channel openers. / Garlid, Keith D.; Paucek, Petr; Yarov-Yarovoy, Vladimir; Sun, Xiaocheng; Schindler, Peter A.

In: Journal of Biological Chemistry, Vol. 271, No. 15, 12.04.1996, p. 8796-8799.

Research output: Contribution to journalArticle

Garlid, KD, Paucek, P, Yarov-Yarovoy, V, Sun, X & Schindler, PA 1996, 'The mitochondrial KATP channel as a receptor for potassium channel openers', Journal of Biological Chemistry, vol. 271, no. 15, pp. 8796-8799.
Garlid, Keith D. ; Paucek, Petr ; Yarov-Yarovoy, Vladimir ; Sun, Xiaocheng ; Schindler, Peter A. / The mitochondrial KATP channel as a receptor for potassium channel openers. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 15. pp. 8796-8799.
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