This study investigates the role of the mitochondrial ATP-sensitive K+ channel (mitoKATP) in response to positive inotropic stress. In Langendorff-perfused rat hearts, inotropy was induced by increasing perfusate calcium to 4 mM, by adding 80 microM ouabain or 0.25 microM dobutamine. Each of these treatments resulted in a sustained increase in rate-pressure product (RPP) of approximately 60%. Inhibition of mitoKATP by perfusion of 5-hydroxydecanoate (5-HD) or tetraphenylphosphonium before induction of inotropic stress resulted in a marked attenuation of RPP. Inhibition of mitoKATP after induction of stress caused the inability of the heart to maintain a high-work state. In human atrial fibers, the increase in contractility induced by dobutamine was inhibited 60% by 5-HD. In permeabilized fibers from the Langendorff-perfused rat hearts, inhibition of mitoKATP resulted, in all cases, in an alteration of adenine nucleotide compartmentation, as reflected by a 60% decrease in the half-saturation constant for ADP [K1/2 (ADP)]. We conclude that opening of cardiac mitoKATP is essential for an appropriate response to positive inotropic stress and propose that its involvement proceeds through the prevention of stress-induced decrease in mitochondrial matrix volume. These results indicate a physiological role for mitoKATP in inotropy and, by extension, in heart failure.

Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoKATP in the response to inotropic stress / GARLID K., D; Puddu, Paolo Emilio; Pasdois, P; COSTA A., D; Beauvoit, B; Criniti, Anna; Tariosse, L; Diolez, P; DOS SANTOS, P.. - In: AMERICAN JOURNAL OF PHYSIOLOGY. HEART AND CIRCULATORY PHYSIOLOGY. - ISSN 0363-6135. - 291:(2006), pp. H152-H160. [10.1152/ajpheart.01233.2005]

Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoKATP in the response to inotropic stress.

PUDDU, Paolo Emilio;CRINITI, ANNA;
2006

Abstract

This study investigates the role of the mitochondrial ATP-sensitive K+ channel (mitoKATP) in response to positive inotropic stress. In Langendorff-perfused rat hearts, inotropy was induced by increasing perfusate calcium to 4 mM, by adding 80 microM ouabain or 0.25 microM dobutamine. Each of these treatments resulted in a sustained increase in rate-pressure product (RPP) of approximately 60%. Inhibition of mitoKATP by perfusion of 5-hydroxydecanoate (5-HD) or tetraphenylphosphonium before induction of inotropic stress resulted in a marked attenuation of RPP. Inhibition of mitoKATP after induction of stress caused the inability of the heart to maintain a high-work state. In human atrial fibers, the increase in contractility induced by dobutamine was inhibited 60% by 5-HD. In permeabilized fibers from the Langendorff-perfused rat hearts, inhibition of mitoKATP resulted, in all cases, in an alteration of adenine nucleotide compartmentation, as reflected by a 60% decrease in the half-saturation constant for ADP [K1/2 (ADP)]. We conclude that opening of cardiac mitoKATP is essential for an appropriate response to positive inotropic stress and propose that its involvement proceeds through the prevention of stress-induced decrease in mitochondrial matrix volume. These results indicate a physiological role for mitoKATP in inotropy and, by extension, in heart failure.
2006
01 Pubblicazione su rivista::01a Articolo in rivista
Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoKATP in the response to inotropic stress / GARLID K., D; Puddu, Paolo Emilio; Pasdois, P; COSTA A., D; Beauvoit, B; Criniti, Anna; Tariosse, L; Diolez, P; DOS SANTOS, P.. - In: AMERICAN JOURNAL OF PHYSIOLOGY. HEART AND CIRCULATORY PHYSIOLOGY. - ISSN 0363-6135. - 291:(2006), pp. H152-H160. [10.1152/ajpheart.01233.2005]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/83293
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