Role of Intracellular Na
            <sup>+</sup>
            Kinetics in Preconditioned Rat Heart

Imahashi, Kenichi; Yoshioka, Jun; Kusuoka, Hideo

doi:10.1161/hh1101.092139

Cited by 26 publications

(15 citation statements)

References 50 publications

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“…Previous studies have proposed that preservation of Na + efflux via Na + /K + -ATPase and limitation of the coupled Ca 2+ influx through NCX during the first minutes of reperfusion contribute importantly to the cardioprotective effects of IPC [4,7,8]. In this study, we demonstrate for the first time that IPC attenuated the dissociation of Na + /K + -ATPase protein from the membrane-cytoskeletal complex and that this effect is mediated through a reduction of calpain activation during reperfusion.…”

Section: Discussionsupporting

confidence: 55%

Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion☆

Inserte

Garcı́a-Dorado

Hernando

et al. 2006

Cardiovascular Research

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Section: Discussionsupporting

confidence: 55%

Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion☆

Inserte

Garcı́a-Dorado

Hernando

et al. 2006

Cardiovascular Research

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“…10 More recently, functional interaction between mitoK ATP channels and Na ϩ /K ϩ -ATPase in preconditioned rat hearts has been reported. 11 Accordingly, our results obtained in the presence of ouabain are of interest and notable. The salient finding is that diazoxide could prevent the ouabain-induced Ca 2ϩ overload in mitochondria.…”

Section: Discussionmentioning

confidence: 64%

Opening of Mitochondrial K _ATP Channels Attenuates the Ouabain-Induced Calcium Overload in Mitochondria

Ishida

Hirota²,

Genka³

et al. 2001

Circulation Research

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2؉] m ) and ⌬⌿ m in rat ventricular myocytes were measured by loading cells with Rhod-2 and JC-1, respectively. Exposure to ouabain (1 mmol/L) for 30 minutes produced mitochondrial Ca 2؉ overload, and the intensity of Rhod-2 fluorescence significantly increased to 173؎16% of baseline (P<0.001). Treatment of myocytes with the mitoK ATP channel opener diazoxide (100 mol/L) blunted the ouabain-induced mitochondrial Ca 2؉ overload (131؎10% of baseline; P<0.001 versus ouabain). Moreover, diazoxide significantly depolarized the ⌬⌿ m and reduced the intensity of JC-1 fluorescence during application of ouabain to 89؎2% of baseline (P<0.05). These effects of diazoxide were blocked by the mitoK ATP channel blocker 5-hydroxydecanoate (500 mol/L). These results indicate that opening of mitoK ATP channels prevents a mitochondrial Ca 2؉ overload in association with ⌬⌿ m depolarization and thereby protects myocardium against ischemic damage. M itochondrial ATP-sensitive Kϩ (mitoK ATP ) channels are thought to play a key role in cardioprotection, 1 but the crucial question remains as to why the opening of mitoK ATP channels can be so protective. Liu et al 2 originally hypothesized that the K ϩ entry through mitoK ATP channels depolarizes the ⌬⌿ m , which reduces the driving force for Materials and Methods Cell PreparationAdult rat ventricular myocytes were isolated by collagenase digestion, as previously described. The Ca 2ϩ fluorophore Rhod-2 was used to measure changes of [Ca 2ϩ ] m . Myocytes were loaded with 10 mol/L Rhod-2 acetoxymethyl ester (Molecular Probes) for 120 minutes at 4°C and then incubated for 30 minutes at 37°C in the culture medium. This two-step cold loading/warm incubation protocol achieves exclusive loading of Rhod-2 into the mitochondria. 6 The ⌬⌿ m was monitored with a fluorescent probe, JC-1 (Molecular Probes). Myocytes were incubated with 0.5 mol/L JC-1 for 10 minutes at 37°C. 7 We verified that the subcellular distribution of fluorescence arising from Rhod-2 and JC-1 was virtually identical to that observed by loading myocytes with the mitochondrial dye rhodamine-123.Myocytes loaded with Rhod-2 and JC-1 were perfused with a HEPES-buffered physiological solution (37°C) containing (mmol/L) NaCl 123, KCl 5, CaCl 2 2.7, MgCl 2 1, HEPES 5, and glucose 5.5 (pH 7.4) and imaged with a Nipkow disk confocal system (CSU10, Yokogawa, Japan), as previously described. 5 Rhod-2 was excited at 488 nm by an argon ion laser, with emission collected above 515 nm through a long-pass barrier filter. JC-1 was excited at 488 nm, and the red emission fluorescence was detected using a long-pass filter of 580 nm. The emission light was imaged through a relay lens to an intensified CCD camera. Images were recorded on a computer (Macintosh 8500/120) at video rate and analyzed with NIH Image 1.62f software. Statistical AnalysisData are expressed as meanϮSEM. Intergroup comparisons are made by Student's t test for two groups and by ANOVA followed by Tukey's test for multiple groups. A value of PϽ0.05 was regarded as significan...

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“…Taken together, these data suggest increased Ca 2ϩ entry via NCX during ischemia in WT hearts. The lack of Ca 2ϩ entry via the reverse-mode NCX would decrease the detrimental effects of Ca 2ϩ overload and better preserve ATP, which would prolong the activity of the Na ϩ /K ϩ -ATPase, 28,29 leading to less Na ϩ accumulation during ischemia in NCX-KO hearts. On reperfusion, the better-preserved ATP in the NCX-KO hearts facilitates Na ϩ extrusion by Na ϩ /K ϩ -ATPase.…”

Section: Ncx During Ischemia Versus Reperfusionmentioning

confidence: 99%

“…On reperfusion, the better-preserved ATP in the NCX-KO hearts facilitates Na ϩ extrusion by Na ϩ /K ϩ -ATPase. 28 31 However, inhibition of NHE reduces the rise in Na ϩ as well as the rise in Ca 2ϩ during ischemia. The rise in Na ϩ has been suggested to have detrimental effects that occur independent of the effects on Ca 2ϩ .…”

Section: Ncx During Ischemia Versus Reperfusionmentioning

confidence: 99%

Cardiac-Specific Ablation of the Na ⁺ -Ca ²⁺ Exchanger Confers Protection Against Ischemia/Reperfusion Injury

Imahashi

Pott

Goldhaber

et al. 2005

Circulation Research

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147

100

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Abstract-During ischemia and reperfusion, with an increase in intracellular Na ϩ and a depolarized membrane potential, Ca 2ϩ may enter the myocyte in exchange for intracellular Na ϩ via reverse-mode Na ϩ -Ca 2ϩ exchange (NCX). To test the role of Ca 2ϩ entry via NCX during ischemia and reperfusion, we studied mice with cardiac-specific ablation of NCX (NCX-KO) and demonstrated that reverse-mode Ca 2ϩ influx is absent in the NCX-KO myocytes. Langendorff perfused hearts were subjected to 20 minutes of global ischemia followed by 2 hours of reperfusion, during which time we monitored high-energy phosphates using 31 P-NMR and left-ventricular developed pressure. In another group of hearts, we monitored intracellular Na ϩ using 23 Na-NMR. Consistent with Ca 2ϩ entry via NCX during ischemia, we found that hearts lacking NCX exhibited less of a decline in ATP during ischemia, delayed ischemic contracture, and reduced maximum contracture. Furthermore, on reperfusion following ischemia, NCX-KO hearts had much less necrosis, better recovery of left-ventricular developed pressure, improved phosphocreatine recovery, and reduced Na ϩ overload. The improved recovery of function following ischemia in NCX-KO hearts was not attributable to the reduced preischemic contractility in NCX-KO hearts, because when the preischemic workload was matched by treatment with isoproterenol, NCX-KO hearts still exhibited improved postischemic function compared with wild-type hearts. Thus, NCX-KO hearts were significantly protected against ischemia-reperfusion injury, suggesting that Ca 2ϩ entry via reverse-mode NCX is a major cause of ischemia/reperfusion injury.

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Role of Intracellular Na ⁺ Kinetics in Preconditioned Rat Heart

Abstract: Abstract-To

Cited by 26 publications

References 50 publications

Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion☆

Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion☆

Opening of Mitochondrial K _ATP Channels Attenuates the Ouabain-Induced Calcium Overload in Mitochondria

Cardiac-Specific Ablation of the Na ⁺ -Ca ²⁺ Exchanger Confers Protection Against Ischemia/Reperfusion Injury

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Role of Intracellular Na + Kinetics in Preconditioned Rat Heart

Abstract: Abstract-To

Cited by 26 publications

References 50 publications

Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion☆

Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion☆

Opening of Mitochondrial K ATP Channels Attenuates the Ouabain-Induced Calcium Overload in Mitochondria

Cardiac-Specific Ablation of the Na + -Ca 2+ Exchanger Confers Protection Against Ischemia/Reperfusion Injury

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Product

Resources

About

Role of Intracellular Na ⁺ Kinetics in Preconditioned Rat Heart

Opening of Mitochondrial K _ATP Channels Attenuates the Ouabain-Induced Calcium Overload in Mitochondria

Cardiac-Specific Ablation of the Na ⁺ -Ca ²⁺ Exchanger Confers Protection Against Ischemia/Reperfusion Injury