Opening of mitochondrial KATP channel occurs downstream of PKC-ε activation in the mechanism of preconditioning

2002 ◽  
Vol 283 (1) ◽  
pp. H440-H447 ◽  
Author(s):  
Yoshito Ohnuma ◽  
Tetsuji Miura ◽  
Takayuki Miki ◽  
Masaya Tanno ◽  
Atsushi Kuno ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Left Ventricle ◽  
Infarct Size ◽  
Katp Channel ◽  
The Other ◽  
Particulate Fraction ◽  
K Channel ◽  
Mitochondrial Katp Channel ◽  
Kinase C

We examined whether the mitochondrial ATP-sensitive K channel (KATP) is an effector downstream of protein kinase C-ε (PKC-ε) in the mechanism of preconditioning (PC) in isolated rabbit hearts. PC with two cycles of 5-min ischemia/5-min reperfusion before 30-min global ischemia reduced infarction from 50.3 ± 6.8% of the left ventricle to 20.3 ± 3.7%. PC significantly increased PKC-ε protein in the particulate fraction from 51 ± 4% of the total to 60 ± 4%, whereas no translocation was observed for PKC-δ and PKC-α. In mitochondria separated from the other particulate fractions, PC increased the PKC-ε level by 50%. Infusion of 5-hydroxydecanoate (5-HD), a mitochondrial KATP blocker, after PC abolished the cardioprotection of PC, whereas PKC-ε translocation by PC was not interfered with 5-HD. Diazoxide, a mitochondrial KATP opener, infused 10 min before ischemia limited infarct size to 5.2 ± 1.4%, but this agent neither translocated PKC-ε by itself nor accelerated PKC-ε translocation after ischemia. Together with the results of earlier studies showing mitochondrial KATP opening by PKC, the present results suggest that mitochondrial KATP-mediated cardioprotection occurs subsequent to PKC-ε activation by PC.

Remifentanil Preconditioning Confers Cardioprotection via  Cardiac κ- and δ-Opioid Receptors

2005 ◽  
Vol 102 (2) ◽  
pp. 371-378 ◽  
Author(s):  
Ye Zhang ◽  
Michael G. Irwin ◽  
Tak Ming Wong ◽  
Mai Chen ◽  
Chun-Mei Cao
Keyword(s):  
At Risk ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Katp Channel ◽  
Area At Risk ◽  
Mitochondrial Katp Channel ◽  
Ringer’S Solution ◽  
Kinase C

Background Remifentanil preconditioning (RPC) reduces the infarct size in anesthetized rat hearts, and this effect seems to be mediated by all three types of opioid receptors (ORs). Because there is evidence of only kappa- and delta- but not mu-ORs in the rat heart, the authors investigated whether RPC confers cardioprotection via cardiac kappa- and delta-OR as well as via extracardiac mu-OR agonist activity. The authors also investigated the involvement of signaling mechanisms, namely protein kinase C and mitochondrial adenosine triphosphate-sensitive potassium (KATP) channels. Methods The hearts of male Sprague-Dawley rats weighing 190-210 g were removed, mounted on a Langendorff apparatus, and perfused retrogradely at 100 cm H2O with Krebs-Ringer's solution. All hearts were subjected to 30 min of ischemia and 2 h of reperfusion. The study consisted of three series of experiments on the effect of ischemic preconditioning or RPC (10, 50, and 100 ng/ml remifentanil) after blockade of OR subtypes (delta-OR antagonist naltrindol, kappa-OR antagonist nor-binaltorphimine, and mu-OR antagonist CTOP). The involvement of protein kinase C or the KATP channel in the cardioprotection of RPC was also investigated using specific blockers in each group. RPC was produced by three cycles of 5-min perfusion of remifentanil in Krebs-Ringer's solution interspersed with a 5-min reperfusion with Krebs solution only. Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining. Results Infarct size as a percentage of the area at risk was significantly reduced after RPC from 51.9 +/- 5.0% (control, n = 8) to 36.2 +/- 10.0% (100 ng/ml RPC, n = 8, P < 0.01). This effect was stopped by pretreatment with naltrindol (52.3 +/- 5.2%) and nor-binaltorphimine (43.5 +/- 6.0%) but not CTOP (37.1 +/- 6.0%). Chelerythrine and GF109203X, both protein kinase C inhibitors, abolished the effects of RPC or ischemic preconditioning on infarct size as a percentage of area at risk. 5-Hydroxydecanoate (a selective mitochondrial KATP channel blocker) also abolished the cardioprotection of RPC and IPC, but HMR-1098 (a selective inhibitor of the sarcolemmal KATP channel) did not. Conclusion Cardiac delta- and kappa- but not mu-ORs mediate the cardioprotection produced by RPC. Both protein kinase C and the mitochondrial KATP channel were involved in this effect.

Brief pressure overload of the left ventricle reduces myocardial infarct size via activation of protein kinase C

2015 ◽  
Vol 78 (9) ◽  
pp. 506-512
Author(s):  
Chia-Yu Tang ◽  
Chang-Chi Lai ◽  
Shu-Chiung Chiang ◽  
Kuo-Wei Tseng ◽  
Cheng-Hsiung Huang
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Left Ventricle ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Pressure Overload ◽  
Myocardial Infarct Size ◽  
Kinase C

Treatment with Sheng-Mai-San Reduces Myocardial Infarct Size Through Activation of Protein Kinase C and Opening of Mitochondrial KATP Channel

2001 ◽  
Vol 29 (02) ◽  
pp. 367-375 ◽  
Author(s):  
Ningyuan Wang ◽  
Shinya Minatoguchi ◽  
Yoshihiro Uno ◽  
Masazumi Arai ◽  
Kazuaki Hashimoto ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Katp Channels ◽  
Myocardial Infarct Size ◽  
Mitochondrial Katp Channel ◽  
Kinase C ◽  
Radix Ginseng ◽  
Mitochondrial Katp Channels

Sheng-Mei-San (SMS), a traditional Chinese formulation comprising Radix Ginseng, Radix Ophiopogonis and Fructus Schisandrae, has long been used for more than 700 years for patients with coronary heart disease. We attempted to clarify 1) whether SMS reduces myocardial infarct size, and 2) whether the infarct size-reducing effect of SMS is related to activation of protein kinase C and the opening of the mitochondrial KATP channels in Japanese white rabbits without collateral circulation. The results indicate that three days treatment but not acute treatment with SMS reduces myocardial infarct size through activation of protein kinase C and opening of the mitochondrial KATP channels.

scholarly journals Modulation of human erg K+channel gating by activation of a G protein-coupled receptor and protein kinase C

1998 ◽  
Vol 511 (2) ◽  
pp. 333-346 ◽  
Author(s):  
Francisco Barros ◽  
David Gómez-Varela ◽  
Cristina G. Viloria ◽  
Teresa Palomero ◽  
Teresa Giráldez ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
G Protein ◽  
Channel Gating ◽  
K Channel ◽  
G Protein Coupled Receptor ◽  
Kinase C ◽  
G Protein Coupled

Volatile Anesthetics Protect the Ischemic Rabbit Myocardium from Infarction

1997 ◽  
Vol 86 (3) ◽  
pp. 699-709 ◽  
Author(s):  
Doris K. Cope ◽  
Keyser W. Impastato ◽  
Michael V. Cohen ◽  
James M. Downey
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Infarct Size ◽  
Adenosine Receptor ◽  
Volatile Anesthetics ◽  
Isolated Hearts ◽  
Anesthetic Agents ◽  
Kinase C ◽  
Adenosine Concentration

Background The influence of anesthetic agents on the infarction process in the ischemic myocardium is unclear. This study evaluated the effects of three intravenous and three inhalational anesthetic agents on myocardial infarction within a quantified ischemic risk zone in rabbit hearts subjected to a standardized regional ischemia-reperfusion insult. Methods Both in vitro and in situ rabbit models were used to investigate the effects of anesthetic agents on infarct size. In all rabbits the heart was exposed and a coronary artery surrounded with a suture to form a snare for subsequent occlusion. In in situ preparations, both intravenous and inhalational agents were tested, whereas only the latter were used in isolated hearts. Infarct size was determined by triphenyltetrazolium chloride staining. To determine whether an adenosine-mediated protective mechanism was involved, 8-(p-sulfophenyl)theophylline, an adenosine receptor blocker, was added to halothane-treated isolated hearts. Adenosine concentration in the coronary effluent was also measured in isolated hearts exposed to halothane. In other protocols, chelerythrine, a highly selective protein kinase C inhibitor, was administered to both halothane-treated and untreated isolated hearts. Results Infarcts in the three in situ groups anesthetized with halothane, enflurane, and isoflurane were about one half as large as infarcts in rabbits that underwent anesthesia with pentobarbital, ketamine-xylazine, or propofol. Volatile anesthetics also protected isolated hearts by a similar amount. Both adenosine receptor blockade and chelerythrine abolished cardioprotection from halothane in isolated hearts. Halothane treatment did not increase adenosine release. Conclusions The volatile anesthetics tested protected the ischemic rabbit heart from infarction, in contrast to the three intravenous agents tested. Protection was independent of the hypotensive effect of the inhalational agents because halothane also protected isolated hearts, in which changing vascular tone is not an issue and coronary perfusion pressure is constant. Cardioprotection by volatile anesthetics depended on both adenosine receptors and protein kinase C, and thus is similar to the mechanism of protection seen with ischemic preconditioning.

Does Ischemic Preconditioning in the Human Involve Protein Kinase C and the ATP-Dependent K + Channel?

1995 ◽  
Vol 77 (5) ◽  
pp. 1030-1035 ◽  
Author(s):  
M. E. Speechly-Dick ◽  
G. J. Grover ◽  
D. M. Yellon
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ischemic Preconditioning ◽  
K Channel ◽  
Kinase C
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