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Titolo:
Long-chain acyl-coenzyme A esters and fatty acids directly link metabolismto K-ATP channels in the heart
Autore:
Liu, GX; Hanley, PJ; Ray, J; Daut, J;
Indirizzi:
Univ Marburg, Inst Physiol, D-35037 Marburg, Germany Univ Marburg Marburg Germany D-35037 t Physiol, D-35037 Marburg, Germany
Titolo Testata:
CIRCULATION RESEARCH
fascicolo: 9, volume: 88, anno: 2001,
pagine: 918 - 924
SICI:
0009-7330(20010511)88:9<918:LAAEAF>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
SENSITIVE POTASSIUM CHANNELS; CARDIOVASCULAR-SYSTEM; MEMBRANE PATCHES; GUINEA-PIG; PIP2; KIR6.2; CELLS; INHIBITION; ACTIVATION; ISCHEMIA;
Keywords:
free fatty acids; acyl-CoA eaters; PIP2; K-ATP channels;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Daut, J Univ Marburg, Inst Physiol, Deutschhausstr 2, D-35037 Marburg, Germany Univ Marburg Deutschhausstr 2 Marburg Germany D-35037 rg, Germany
Citazione:
G.X. Liu et al., "Long-chain acyl-coenzyme A esters and fatty acids directly link metabolismto K-ATP channels in the heart", CIRCUL RES, 88(9), 2001, pp. 918-924

Abstract

ATP-sensitive K (K-ATP) channels are inhibited by cytosolic ATP, a defining property that implicitly links these channels to cellular metabolism. Here we report a direct link between fatty acid metabolism and K-ATP channels in cardiac muscle cells. Long-chain (LC) acyl-coenzyme A (CoA) esters are synthesized from fatty acids and serve as the principal metabolic substratesof the heart. We have studied the effects of LC acyl-CoA esters and LC fatty acids on K-ATP channels of isolated guinea pig ventricular myocytes and compared them with the effects of phosphatidylinositol 4,5-bisphosphate (PIP2). Application of oleoyl-CoA (0.2 or 1 mu mol/L), a naturally occurring acyl-CoA ester, to the cytosolic side of excised patches completely prevented rundown of K-ATP channels, but not of Kir2 channels. The open probabilityof K-ATP channels measured in the presence of oleoyl-CoA or PIP2 was voltage dependent, increasing with depolarization. Oleoyl-CoA greatly reduced the ATP sensitivity of K-ATP channels. At a concentration of 2 mu mol/L, oleoyl-CoA increased the half-maximal inhibitory concentration of ATP > 200-fold. The time course of the decrease in ATP sensitivity was much faster during application of oleoyl-CoA than during application of PIP2. The effects ofPIP2, but not of oleoyl-CoA, were inhibited by increasing Ca2+ to 1 mmol/L. Oleate (C18:1; 10 mu mol/L), the precursor of oleoyl-CoA, inhibited K-ATPchannels activated by oleoyl-CoA. Palmitoleoyl-CoA and palmitoleate (C16:1) exerted similar reciprocal effects. These findings indicate that LC fattyacids and their CoA-linked derivatives may be key physiological modulatorsof K-ATP channel activity in the heart.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 18:31:52