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Mitochondrial KATP channels participate in the limitation of infarct size by cariporide

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Abstract

The objective of this study is to assess the participation of mitochondrial ATP-sensitive potassium (mitoKATP) channels in the cardioprotective effects of the Na+/H+ exchanger (NHE-1) blocker cariporide in isolated rat hearts. Regional ischemia was induced by occlusion of left anterior descending coronary artery during 40 min followed by 2-h reperfusion (IC). Cariporide (C, 10 μΜ), or C plus 5-hydroxydecanoate (5-HD, 100 μM, a selective mitoKATP channel inhibitor), or C plus chelerythrine (Chele, 1 μM, a PKC inhibitor), or an opener of mitoKATP channels, diazoxide (Dz, 100 μM) was applied at the onset of reperfusion. Infarct size (IS) and myocardial function were evaluated. The calcium-induced permeability transition pore (mPTP) opening was determined by measuring the light scattering decrease (LSD, a.u.) in isolated mitochondria in the absence and presence of C, C + 5-HD and Dz. IS was 33 ± 2% of the risk area in IC and was significantly diminished by C (15 ± 2%, p < 0.05), which also improved myocardial function [LVDP = 58 ± 5% (IC) vs 80 ± 5% (C)] and blunted LSD [0.80 ± 0.04 (IC) vs 0.51 ± 0.04 (C) a.u.]. 5-HD and Chele were both able to abolish the cardioprotective effects of C on IS. Dz treatment decreased IS and LSD to a similar extent to that produced by C (15 ± 4% and 0.52 ± 0.04 a.u., respectively). The present data suggest that attenuation of mPTP opening after PKC-mediated mitoKATP channel activation is a crucial step for the cardioprotective effects of cariporide.

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Acknowledgments

This work was supported in part by the grant PICT 1046 from Agencia Nacional de Promoción Científica y Técnica of Argentina to Dr Susana M Mosca.

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Authors and Affiliations

  1. Fellowship of CONICET, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, 1900, La Plata, Argentina

    Ignacio Pérez Nuñez & Juliana Fantinelli

  2. Fellowship of ANPCYT, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina

    Luisa F. González Arbeláez

  3. Established Investigator of CONICET, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina

    Susana M. Mosca

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  1. Ignacio Pérez Nuñez
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  2. Juliana Fantinelli
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  3. Luisa F. González Arbeláez
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  4. Susana M. Mosca
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Correspondence to Susana M. Mosca.

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Nuñez, I.P., Fantinelli, J., Arbeláez, L.F.G. et al. Mitochondrial KATP channels participate in the limitation of infarct size by cariporide. Naunyn-Schmiedeberg's Arch Pharmacol 383, 563–571 (2011). https://doi.org/10.1007/s00210-011-0632-z

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