Role of mitochondrial permeability transition pore and mitochondrial ATP-sensitive potassium channels in the protective effects of ischemic preconditioning in isolated hearts from fed and fasted rats

MARINA PRENDES MG1,2, HERMANN R, TORRESIN ME, VÉLEZ D, SAVINO EA, VARELA A.

JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY

SERVICIO PUBLICACIONES UNIVERSIDAD NAVARRA

Lugar: Navarra; Año: 2014 vol. 70 p. 791 - 800

1138-7548

The aim of the present study was to assess whether the protective effects of ischemic preconditioning (PC) are associated with activation of the mitochondrial ATP-sensitive potassium channels (mitoKATP) and if there is any relationship between the activity of these channels and the mitochondrial permeability transition pore (MPTP) opening in ischemic-reperfused rat hearts under different nutritional conditions. Langendorff-perfused hearts of fed and 24-h fasted rats were exposed to 25 min of no-flow global ischemia plus 30 min of reperfusion. Fasting accelerated functional recovery and attenuated MPTP opening. The mitoKATP blocker, 5-hydroxydecanoic (HD), did not influence functional recovery and MPTP opening induced by ischemia?reperfusion in the fed hearts but partially reversed the beneficial effects of fasting. PC and the mitoKATP opener, diazoxide (DZ), improved functional recovery, preserved cell viability, and inhibited MPTP opening in both fed and fasted hearts. The protection elicited by PC and DZ on contractile recovery and MPTP opening was reversed by HD, which did not affect cell viability. Altogether, these results argue for a role of mitoKATP and its impact on preservation mitochondrial inner membrane permeability as a relevant factor in the improvement of contractile function in the ischemic-reperfused rat heart. They also suggest that the functional protection elicited by PC may be related to this mechanism.