Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles.

Kihara, Yasuki; Sasayama, Shígetake; Inoko, Moriaki; Morgan, James P.

doi:10.1172/jci117082

Cited by 16 publications

(6 citation statements)

References 63 publications

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“…Intracellular Ca 2ϩ and Ca 2ϩ uptake increases markedly during ischemia-reperfusion (27,42,44) and during reoxygenation of hypoxic cardiomyocytes (14,34,35,39). These changes, which are often referred to as Ca 2ϩ overload, have been associated with cell damage.…”

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confidence: 99%

Effect of extracellular Mg²⁺on ROS and Ca²⁺accumulation during reoxygenation of rat cardiomyocytes

Sharikabad¹,

Østbye²,

Lyberg³

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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The effects of Mg(2+) on reactive oxygen species (ROS) and cell Ca(2+) during reoxygenation of hypoxic rat cardiomyocytes were studied. Oxidation of 2',7'-dichlorodihydrofluorescein (DCDHF) to dichlorofluorescein (DCF) and of dihydroethidium (DHE) to ethidium (ETH) within cells were used as markers for intracellular ROS levels and were determined by flow cytometry. DCDHF/DCF is sensitive to H(2)O(2) and nitric oxide (NO), and DHE/ETH is sensitive to the superoxide anion (O(2)(-).), respectively. Rapidly exchangeable cell Ca(2+) was determined by (45)Ca(2+) uptake. Cells were exposed to hypoxia for 1 h and reoxygenation for 2 h. ROS levels, determined as DCF fluorescence, were increased 100-130% during reoxygenation alone and further increased 60% by increasing extracellular Mg(2+) concentration to 5 mM at reoxygenation. ROS levels, measured as ETH fluorescence, were increased 16-24% during reoxygenation but were not affected by Mg(2+). Cell Ca(2+) increased three- to fourfold during reoxygenation. This increase was reduced 40% by 5 mM Mg(2+), 57% by 10 microM 3,4-dichlorobenzamil (DCB) (inhibitor of Na(+)/Ca(2+) exchange), and 75% by combining Mg(2+) and DCB. H(2)O(2) (25 and 500 microM) reduced Ca(2+) accumulation by 38 and 43%, respectively, whereas the NO donor S-nitroso-N-acetyl-penicillamine (1 mM) had no effect. Mg(2+) reduced hypoxia/reoxygenation-induced lactate dehydrogenase (LDH) release by 90%. In conclusion, elevation of extracellular Mg(2+) to 5 mM increased the fluorescence of the H(2)O(2)/NO-sensitive probe DCF without increasing that of the O(2)(-).-sensitive probe ETH, reduced Ca(2+) accumulation, and decreased LDH release during reoxygenation of hypoxic cardiomyocytes. The reduction in LDH release, reflecting the protective effect of Mg(2+), may be linked to the effect of Mg(2+) on Ca(2+) accumulation and/or ROS levels.

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confidence: 99%

Effect of extracellular Mg²⁺on ROS and Ca²⁺accumulation during reoxygenation of rat cardiomyocytes

Sharikabad¹,

Østbye²,

Lyberg³

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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“…Moreover, it is not likely that NiCh may have caused a reversal of intracellular Ca 2+ for extracellular Na+ exchange, which could also contribute to the observed rise in [Ca 2"1I. Such reversal requires much higher NiCh concentration than the micromolar level used in these experiments (27). Rapid depolarization of the renal tubule cells by transient increases in extracellular [K"1 also resulted in increases in [Ca 2"1I.…”

Section: Discussionmentioning

confidence: 80%

Hypoxic Rise in Cytosolic Calcium and Renal Proximal Tubule Injury Mediated by a Nickel-Sensitive Pathway

Barac‐Nieto

Constantinescu²,

Pina-Benabou

et al. 2004

Exp Biol Med (Maywood)

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In the kidney, cell injury resulting from ischemia and hypoxia is thought to be due, in part, to increased cytosolic Ca(2+) levels, [Ca(2+)]i, leading to activation of lytic enzymes, cell dysfunction, and necrosis. We report evidence of a progressive and exponential increase in [Ca(2+)]i (from 245 +/- 10 to 975 +/- 100 nM at 45 mins), cell permeabilization and propidium iodide (PI) staining of the nucleus, and partial loss of cell transport functions such as Na(+)-gradient-dependent uptakes of (14)C-alpha-methylglucopyranoside and inorganic phosphate ((32)Pi) in proximal convoluted tubules of adult rabbits subjected to hypoxia. The rise in [Ca(2+)]i depended on the presence of extracellular [Ca(2+)] and could be blocked by 50 microM Ni(2+)but not by verapamil (100 microM). Presence of 50 microM Ni(2+) also reduced the hypoxia-induced morphological and functional injuries. We also used HEK 293 cells, a kidney cell line, incubated in media without glucose and exposed for 3.5 hrs to 1% O(2)-5% CO(2) and then returned to glucose-containing media for another 3.5 hrs in an air-5% CO(2) atmosphere and finally exposed for 1 min to media containing 1 microM PI. NiCl(2) (50 microM) or pentobarbital (300 microM) more than phenobarbital (1.5 mM), when present in the incubation medium during both the hypoxic and the reoxygenation periods, induced significant (P < 0.001) reductions in the number of cell nuclei stained with PI, similar to their relative potency as inhibitors of T channels. Our findings indicate that hypoxia-induced alterations in calcium level and subsequent cell injury in the proximal convoluted tubule and in HEK cells involve a nickel-sensitive and dihydropyridine insensitive pathway or channel.

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“…The high intracellular calcium concentration accumulated during the ischaemic period represents the trigger for cellular contracture during reperfusion. With the onset of reperfusion, intracellular calcium may increase even further by calcium influx via the Na ; -Ca 2; exchanger [25], and phasic oscillations of intracellular calcium occur as a result of pathological calcium cycling the the sarcoplasmic reticulum [26]; both mechanisms can increase further contractile activation. In normal myocardium, inhibition of the Na ; -Ca 2; exchanger by halothane has been shown [27].…”

Section: Interpretation Of Resultsmentioning

confidence: 99%

Effect of halothane on myocardial reoxygenation injury in the isolated rat heart

Schlack¹,

Hollmann²,

Stunneck³

et al. 1996

British Journal of Anaesthesia

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Several studies have reported a protective effect of halothane on myocardial injury in an ischaemia-reperfusion situation. It is unclear if the protection is a result of the haemodynamic effects of halothane or if halothane has a specific action on ischaemia or reperfusion pathomechanisms. To examine this question, we have used an isolated rat heart model where heart rate (300 beat min-1), ventricular volume and coronary flow are constant. Left ventricular developed pressure (LVDP) and release of creatine kinase (CK) were measured as variables of myocardial performance and cellular injury, respectively. Five control hearts were subjected to 35 min of low-flow (2 ml min-1) anoxic and substrate-free perfusion and were then perfused for 1 h with the oxygenated buffer. In the treatment groups, halothane 0.4 mmol litre-1 was added during the first 30 min of anoxic perfusion (n = 5) or during the first 30 min of reoxygenation (n = 5). In five additional hearts, the effect of halothane 0.4 mmol litre-1 was tested under normoxic conditions. Mean basal CK release was 0.29 (SEM 0.13) iu g-1 min-1 and LVDP was 105.5 (4.0) mm Hg. Under normoxic conditions, halothane reduced LVDP to 52.0 (2.6) mm Hg. In control hearts, the major cell injury occurred at the onset of reoxygenation (CK release increased to 149.1 (9.1) iu g-1 min-1) and functional recovery after 1 h of reoxygenation was poor (control LVDP, 14.2(2.)% of baseline). Halothane during anoxia attenuated myocardial injury only moderately (CK release 50.2(5.7) iu g-1 min-1) and LVDP recovered to 30.8(3.0)% (each P < 0.05 vs control). When halothane was administered at reoxygenation, CK release was reduced to 10.1 (0.9) iu g-1 min-1 and LVDP recovered to 69.4(4.9)% (each P < .05 vs control). We conclude that halothane not only attenuated ischaemic injury but had a specific protective action against reoxygenation injury.

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Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles.

Cited by 16 publications

References 63 publications

Effect of extracellular Mg²⁺on ROS and Ca²⁺accumulation during reoxygenation of rat cardiomyocytes

Effect of extracellular Mg²⁺on ROS and Ca²⁺accumulation during reoxygenation of rat cardiomyocytes

Hypoxic Rise in Cytosolic Calcium and Renal Proximal Tubule Injury Mediated by a Nickel-Sensitive Pathway

Effect of halothane on myocardial reoxygenation injury in the isolated rat heart

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Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles.

Cited by 16 publications

References 63 publications

Effect of extracellular Mg2+on ROS and Ca2+accumulation during reoxygenation of rat cardiomyocytes

Effect of extracellular Mg2+on ROS and Ca2+accumulation during reoxygenation of rat cardiomyocytes

Hypoxic Rise in Cytosolic Calcium and Renal Proximal Tubule Injury Mediated by a Nickel-Sensitive Pathway

Effect of halothane on myocardial reoxygenation injury in the isolated rat heart

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Effect of extracellular Mg²⁺on ROS and Ca²⁺accumulation during reoxygenation of rat cardiomyocytes

Effect of extracellular Mg²⁺on ROS and Ca²⁺accumulation during reoxygenation of rat cardiomyocytes