ATP-sensitive potassium channel mediates delayed ischemic protection by heat stress in rabbit heart

Abstract

Heat shock protects against myocardial ischemia-reperfusion injury possibly via increased expression of heat shock proteins. The direct evidence of heat shock protein protection in vivo remains circumstantial, and no other new mechanism of protection has been proposed. Recent studies suggest that opening of ATP-sensitive K+ channels (KATP channels) plays an important role in ischemic preconditioning; however, it is not known whether this channel is also important in delayed protection conferred by heat shock. Anesthetized rabbits underwent heat shock treatment by raising core temperature to 42°C for 15 min. Twenty-four hours later, the animals were reanesthetized and subjected to regional ischemia-reperfusion. The specific KATP channel blockers glibenclamide (0.3 mg/kg ip) and sodium 5-hydroxydecanoate (5HD; 5 mg/kg iv) were used to block the channel function. The drugs were administered at two different times, either pre-heat stress or preischemia. Infarct size was determined by triphenyltetrazolium chloride staining. The 72-kDa heat shock protein (HSP 72) was measured by Western blots. Our results show that heat shock produced a marked reduction in infarct size (39.4 ± 8.1 to 14.3 ± 2.5% of risk area, P < 0.05). Glibenclamide and 5HD completely abolished heat shock-induced reduction in infarct size (42.3 ± 0.32 and 33.7 ± 4.8%) when given before ischemia-reperfusion; however, these antagonists failed to block protection when administered before the onset of heat shock. Furthermore, the enhanced expression of HSP 72 in heat shock groups was not diminished by glibenclamide or 5HD, suggesting a lack of a direct role of this protein in conferring cardiac protection by heat shock. The complete blockade of cardiac protection by glibenclamide and 5HD strongly suggests that opening of this channel is a very important component of heat shock-induced ischemic protection in rabbit hearts.

Failure to confer cardioprotection and to increase the expression of heat-shock protein 70 by preconditioning with a ?-opioid receptor agonist during ischaemia and reperfusion in streptozotocin-induced diabetic rats

“…The impaired channels could be linked to the failure to enhance HSP expression in diabetes. However, it has been shown in the rabbit that heat stress confers cardioprotection and that blockade of the K ATP channels with their blockers during ischaemia and reperfusion abolishes the effect of heat stress on cardioprotection, but not on HSP72 expression [5], indicating the cardioprotective action of HSP might not directly link to the channels. We have also shown that PKC-ε mediates delayed cardioprotection of UP [21].…”

HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts

“…These improvements in energy metabolism with heat shock treatment of hearts before I/R are associated with enhanced recovery in myocardial performance and reduced I/R injury. Also, a decrease in the duration of cardiomyocyte action potentials secondary to an increase in activity of ATP-sensitive potassium channels (12,27) and diminished accumulation of intracellular Ca 2ϩ (45) with resulting reduced Ca 2ϩ sensitivity (22) have been reported to be induced by heat stress and to limit I/R injury.…”

Protein kinase Cϵ interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning

“…Reactions were terminated by the addition of SDS Laemmli sample buffer at 90 • C. Samples were then heated for 5 min and subjected to SDS/PAGE. [8][9][10][11][12][13][14][15][16][17]] These peptides were then conjugated to the protein transducing domain of the HIV-Tat protein (amino acids 47-57) as described previously [37]. An HIV-Tat carrier-carrier peptide (YGRKKRRQRRR-YGRKKRRQRRR) was synthesized as a control.…”

“…Experimentally, it is the most powerful form of cardiac protection known and it has been demonstrated in cardiac myocytes [2][3][4][5], intact hearts [6,7] and many animal species [8][9][10][11], including humans [12][13][14]. Downstream signalling molecules reported to be involved in PC include ATPdependent potassium channels [4,12,15,16], PKC (protein kinase C) isoenzymes [2, 3,12,15,17,18], MAPK (mitogen-activated protein kinase) enzymes [19][20][21], tyrosine kinases [22][23][24], PI3K (phosphoinositide 3-kinase) [22,25], heat-shock proteins [5,16,26], nitric oxide [27][28][29], free radicals [21,25,30] etc.…”