ISSN 0326-646X





Sumario Vol. 42 - Nº 1 Enero - Marzo 2013

Ischemic preconditioning: are the sarcolemmal, the mitochondrial or both KATP channels the good guys?

Irene L. Ennis

Centro de Investigaciones Cardiovasculares.
Facultad de Ciencias Médicas.
Calle 60 y 120. (1900) La Plata. Buenos Aires, Argentina.
Correo electrónico

Los autores de este trabajo declaran al mismo no afectado por conflictos de interés.
Rev Fed Arg Cardiol. 2013; 42(1): 1-2

Print version Imprimir sólo la columna central


In 1986, Murry et al [1], published a seminal investigation in which they described for the first time, the ischemic preconditioning (IP) phenomenon in a canine model of ischemia/reperfusion. They showed that several brief ischemic episodes followed by reperfusion conducted prior to the event of prolonged ischemia could significantly decrease the extent of infarction in comparison to that occurring when the heart was subjected to prolonged ischemia only. Subsequent papers not only confirmed this finding in different experimental animal models and even in human beings [2], but they also proved that IP besides reducing the size of infarction and improving contractile recovery, was also efficient in decreasing the reperfusion arrhythmias, just as the work by Lascano et al showed, published in this issue of the Journal. See the paper published.

IP promotes two phases of myocardial protection. The first one, called early IP or “first window”, protects the heart for one or two hours and then it disappears; the second one, called late IP or “second window” of protection appears 24 hours after performing the IP protocol and it may last for up to 3 days.

At the beginning of the 1990s, it was gradually understood that the protection given by the IP would be due to the activation of intracellular signaling pathways, in which the opening of the ATP-dependent K (KATP) channels of the sarcolemma and/or the mitochondrial internal membrane seems to play a critical role. It is currently agreed that the protection occurs early during reperfusion when the intracellular signaling pathways prevent the lethal opening of the mitochondrial transition pores that leads to the mitochondria uncoupling and the destruction of the cardiomyocytes during the first minutes of reperfusion [3,4]. In their current work, Lascano et al proposed that the opening of sarcolemmal KATP channels, and possibly mitochondrial to a lesser extent, is an effector mechanism of protection against the reperfusion arrhythmias in a large and conscious mammal model. They reached this conclusion through the analysis of the results obtained by the pharmacological inhibition of these ion channels. This is a point that deserves to be considered, since the drugs used are not all completely selective for the different KATP channels, and nor do they luck unspecific effects [5-7].

It is interesting to highlight that recent works show strong evidence supporting that the opening of mitochondrial KATP channels would be critical to trigger the protective effect of preconditioning before the injury by ischemia and reperfusion. The opening of these channels would lightly alkalize the mitochondrial matrix, dispelling the transmembrane potential and fostering the release of reactive species derived from oxygen that would dispel the protection [8,9].

From what was presented, there is no doubt that performing future experiments in which the specific inhibition of KATP channels is achieved, will help to clarify the real participation of each of these mediators in the IP phenomenon. In this regard, the use of molecular biology techniques such as RNA interference to decrease the expression of channels would be very useful. This is only now a real possibility, since the recent identification of the molecular composition of the mitochondrial KATP channel pore by the O’Rourke group from Baltimore [10].



  1. Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74: 1124-1136.
  2. Napoli C, Liguori A, Chiariello M, et al. New-onset angina preceding acute myocardial infarction is associated with improved contractile recovery after thrombolysis. Eur Heart J 1998;19: 411-419.
  3. Hausenloy DJ, Yellon DM. New directions for protecting the heart against ischaemia-reperfusion injury: Targeting the reperfusion injury salvage kinase (risk)-pathway. Cardiovasc Research 2004; 61: 448-460.
  4. Yang X, Cohen MV, Downey JM. Mechanism of cardioprotection by early ischemic preconditioning. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy 2010; 24: 225-234.
  5. Hanley PJ, Gopalan KV, Lareau RA, et al. Beta-oxidation of 5-hydroxydecanoate, a putative blocker of mitochondrial atp-sensitive potassium channels. J Physiol 2003; 547: 387-393.
  6. Grimmsmann T, Rustenbeck I. Direct effects of diazoxide on mitochondria in pancreatic b-cells and on isolated liver mitochondria. British J Pharmacol 1998; 123: 781-788.
  7. Lim KH, Javadov SA, Das M, et al. The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration. J Physiol 2002; 545: 961-974.
  8. Oldenburg O, Qin Q, Krieg T, et al. Bradykinin induces mitochondrial ros generation via no, cgmp, pkg, and mitokatp channel opening and leads to cardioprotection. Am J Physiol 2004; 286: H468-476.
  9. Cohen MV, Yang XM, Liu Y, et al. Cardioprotective pkg-independent no signaling at reperfusion. Am J Physiol 2010; 299: H2028-2036.
  10. Foster DB, Ho AS, Rucker J, et al. Mitochondrial romk channel is a molecular component of mitok(atp). Circulation Research 2012; 111: 446-454.


Publication: March 2013

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XXXI Congreso Nacional de Cardiología

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