5-Hydroxydecanoate and coenzyme A are inhibitors of native sarcolemmal KATP channels in inside-out patches

Biochimica Et Biophysica Acta
Xiantao LiPeter J Hanley

Abstract

5-Hydroxydecanoate (5-HD) inhibits preconditioning, and it is assumed to be a selective inhibitor of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels. However, 5-HD is a substrate for mitochondrial outer membrane acyl-CoA synthetase, which catalyzes the reaction: 5HD + CoA + ATP --> 5-HD-CoA (5-hydroxydecanoyl-CoA) + AMP + pyrophosphate. We aimed to determine whether the reactants or principal product of this reaction modulate sarcolemmal K(ATP) (sarcK(ATP)) channel activity. Single sarcK(ATP) channel currents were measured in inside-out patches excised from rat ventricular myocytes. In addition, sarcK(ATP) channel activity was recorded in whole-cell configuration or in giant inside-out patches excised from oocytes expressing Kir6.2/SUR2A. 5-HD inhibited (IC(50) approximately 30 microM) K(ATP) channel activity, albeit only in the presence of (non-inhibitory) concentrations of ATP. Similarly, when the inhibitory effect of 0.2 mM ATP was reversed by 1 microM oleoyl-CoA, subsequent application of 5-HD blocked channel activity, but no effect was seen in the absence of ATP. Furthermore, we found that 1 microM coenzyme A (CoA) inhibited sarcK(ATP) channels. Using giant inside-out patches, which are weakly sensitive to "contamin...Continue Reading

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Citations

Feb 3, 2012·Analytical Chemistry·Joe F LoDavid T Eddington
Jul 29, 2010·Physiological Reviews·Thomas P FlaggColin G Nichols
Jun 25, 2013·Pharmacology & Therapeutics·William A Coetzee
Mar 10, 2016·Biochimica Et Biophysica Acta·Michał LaskowskiAdam Szewczyk
Oct 24, 2015·The European Respiratory Journal·Natascha SommerNorbert Weissmann
Apr 3, 2014·Physiological Reviews·Ildiko Szabo, Mario Zoratti
Jun 10, 2015·Medicine and Science in Sports and Exercise·Jasenka KraljevicJasna Marinovic
Dec 15, 2015·Physiological Reviews·Monique N Foster, William A Coetzee
Jan 26, 2012·Anesthesiology·Hiroyuki Kinoshita, Naoyuki Matsuda

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