Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake.

Kaplán, Peter; Hendrikx, Marc; Mattheussen, M; Mubagwa, Kanigula; Flameng, Willem

doi:10.1161/01.res.71.5.1123

Cited by 68 publications

(25 citation statements)

References 42 publications

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“…35 Recovery of the amplitude of Ca 2+ transients was also mainly mediated by restoration of SR Ca 2+ uptake and Ca 2+ stores. 25,26 In the present study, untreated hearts still exhibited a higher diastolic [Ca 2+ ]i early reperfusion. More rapid decline (normalization) of diastolic [Ca 2+ ]i in the KBR-treated heart might also be a consequence of the inhibitory effect of this agent on the NCX.…”

Section: Effects Of the Ncx Inhibitor On [Ca 2+ ]I During Ischemia Ansupporting

confidence: 42%

“…Assessment of intracellular Ca 2+ kinetics using rapid caffeine application indicated that reduction of SR Ca 2+ stores occurs during anoxia, 25 and an ischemiainduced reduction of SR Ca 2+ uptake was demonstrated using a biochemical assay. 26 It is unlikely that KBR modified SR dysfunction during ischemia.…”

Section: Effects Of the Ncx Inhibitor On [Ca 2+ ]I During Ischemia Anmentioning

confidence: 99%

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Inhibition by KB-R7943 of the Reverse Mode of the Na+/Ca2+ Exchanger Reduces Ca2+ Overload in Ischemic-Reperfused Rat Hearts.

Seki

Taniguchi

Takeda

et al. 2002

Circ J

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Publication No. 85-23, revised 1996). Adult male Sprague-Dawley rats weighing 300-350 g were anesthetized with pentobarbital Na (30 mg/kg, ip). The heart was quickly isolated and the aorta was cannulated for retrograde Langendorff perfusion. N-2-hydroxy-ethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered Tyrode solution (140 mmol/L NaCl, 6 mmol/L KCl, 1 mmol/L MgCl2, 2 mmol/L CaCl2, 10 mmol/L HEPES, 10 mmol/L J 2002; 66: 390 -396 (Received September 28, 2001; revised manuscript received January 9, 2002; accepted January 11, 2002 ]i dynamics and left ventricular pressure were monitored in perfused beating hearts. The effects of KB-R7943 (KBR), a selective inhibitor of the NCX in the reverse mode, were analyzed during low-Na + exposure and ischemia -reperfusion. Hearts from Sprague-Dawley rats were retrogradely perfused and loaded with 4 mol/L fura-2 to measure the fluorescence ratio as an index of [Ca 2+ ]i. To evaluate KBR effects on the reverse mode exchanger, the increase in [Ca 2+ ]i induced by low-Na + exposure (Na + : 30 mmol/L, 10 mmol/L caffeine pre-treatment) was measured with and without 10 mol/L KBR (n=5). In another series, the hearts were subjected to 10 min of low-flow ischemia with pacing, followed by reperfusion in the absence (n=6) or in the presence of 10 mol/L KBR (n=6). Background autofluorescence was subtracted to estimate the ratio in the ischemia -reperfusion protocol. KBR significantly suppressed the increase in [Ca 2+ ]i induced by low-Na + (40.2±11.2% of control condition, p=0.014), as well as on increase in diastolic [Ca 2+ ]i during ischemia (% increase from pre-ischemia in [Ca 2+ ]i at 10 min: KBR, 17.9±6.4%; no KBR, 44.4±7.7%; p=0.024). After reperfusion, diastolic [Ca 2+ ]i normalized more rapidly in KBR-treated hearts (% increase at 1 min: KBR, 4.5±7.0%; no KBR, 39.8±12.2%; p=0.03). Treatment with KBR also accelerated recovery of the rate -pressure product on reperfusion (1 min: KBR, 8,944±1,554 min -1 ·mmHg; no KBR, 4,970±1,325; p<0.05). Thus, inhibition of the reverse mode exchanger by KBR reduced ischemic Ca 2+ overload and possibly improved functional myocardial recovery during reperfusion in a whole heart model. (Circ J 2002; 66: 390 -396) Circ

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Section: Effects Of the Ncx Inhibitor On [Ca 2+ ]I During Ischemia Ansupporting

confidence: 42%

Section: Effects Of the Ncx Inhibitor On [Ca 2+ ]I During Ischemia Anmentioning

confidence: 99%

Inhibition by KB-R7943 of the Reverse Mode of the Na+/Ca2+ Exchanger Reduces Ca2+ Overload in Ischemic-Reperfused Rat Hearts.

Seki

Taniguchi

Takeda

et al. 2002

Circ J

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“…20) During ischaemia-reperfusion, the deleterious increase in intracellular Ca 2+ concentration appears to result from the reverse operation of the Na + /Ca 2+ exchange mechanism associated with intracellular acidosis and membrane depolarization as well as impaired sarco-endoplasmic reticulum (SR) Ca 2+ -ATPase2 (SERCA2a), which is responsible for SR Ca 2+ uptake. 21,22) Factors that diminish the increase in intracellular Ca 2+ would be expected to attenuate myocardial injury, so downregulation of Ca 2+ channels should be beneficial. Physiologically, the expression of LTCC mRNA was transient decreased soon after myocardial infraction followed by recovery towards normal level in a 4-week follow-up period.…”

Section: Discussionmentioning

confidence: 99%

Effects of <i>Leonurine</i> on L-Type Calcium Channel in Rat Ventricular Myocytes

Hong

Wang

et al. 2012

Biological & Pharmaceutical Bulletin

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Leonurine (Leo) is a special alkaloid principle of Herba leonuri that has recently been suggested to improve cardiovascular functions. To date, there is no direct ionic evidence of Leo on regulating calcium channels in the heart. In the present study, we examined the effects of Leo on action potentials and membrane currents recorded from isolated rat ventricular myocytes with the whole-cell patch clamp technique. Leo 100 µM shortened the action potential duration in a dose-dependent manner. Leo up to 200 µM had no significant effect on the Na current (I Na ) and K current (I K ). However, Leo depressed the L-type Ca 2 current (I Ca,L ). In the presence of 20 and 100 µM Leo, the current density was decreased and the voltage at half maximal inactivation V 0.5 shift to more negative potential. The recovery time constant was also delayed. In addition, the transcription and protein expression levels of L-type calcium channel (Ca v1.2 ) in primary cultured neonatal myocytes from Sprague-Dawley rats were reduced by Leo treatment in a dose-dependent fashion as assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assays. We conclude that Leo inhibits L-type calcium channels in cardiomyocytes.

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“…ATPase 2a (SERCA2a), which is primarily responsible for sarcoplasmic reticulum Ca 2+ uptake, was reported to be decreased in protein level or activity in the ischemic myocardium in various animals and humans (4)(5)(6)(7). Additionally, vectormediated gene transfer to increase SERCA2a expression or the use of transgenic animals with SERCA2a overexpression have clearly established the potential beneficial effects in ischemic heart, and thus promoted the field of potential SERCA2a gene therapy in IHD (8)(9)(10)(11).…”

Section: +mentioning

confidence: 99%

Attenuation of Endoplasmic Reticulum Stress-Related Myocardial Apoptosis by SERCA2a Gene Delivery in Ischemic Heart Disease

Wei

et al. 2010

Mol Med

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Previous studies suggested that endoplasmic reticulum (ER) stress-associated apoptosis plays an important role in the pathogenesis of ischemic heart disease. Gene transfer of sarco/endoplasmic reticulum Ca 2+ ATPase 2a (SERCA2a) attenuates myocardial apoptosis in a variety of heart failure models. This study is to investigate the effects of SERCA2a gene delivery on the myocardial apoptosis and ER stress pathway in a porcine ischemic heart disease model. Eighteen pigs were either subjected to ameroid implantation in the coronary artery or sham operation. Eight wks after gene delivery, the protein level and activity of SERCA2a were measured. Myocardial apoptosis was determined using terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling assay. Regional myocardial perfusion and function were evaluated by 99m Tc-sestamibi ( 99m Tc-MIBI) single photon emission computed tomography and echocardiography. The ER stress signaling was assessed by Western blot. SERCA2a protein level and activity were significantly decreased in the ischemic myocardium and restored to normal after SERCA2a gene transfer. Restoration of SERCA2a expression significantly improved the cardiac function, although no improvement of regional myocardial perfusion was detected. Restoration of SERCA2a significantly attenuated myocardial apoptosis and reversed the activation of unfolded protein response (UPR) pathway and the ER stress-associated apoptosis pathways. These findings demonstrate a robust role of SERCA2a in attenuation of ischemic myocardial apoptosis, correlating with reverse activation of the ER stress-associated apoptosis pathways, suggesting that the beneficial effects of SERCA2a gene transfer may involve the attenuation of ER stress-associated myocardial apoptosis.

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Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake.

Cited by 68 publications

References 42 publications

Inhibition by KB-R7943 of the Reverse Mode of the Na+/Ca2+ Exchanger Reduces Ca2+ Overload in Ischemic-Reperfused Rat Hearts.

Inhibition by KB-R7943 of the Reverse Mode of the Na+/Ca2+ Exchanger Reduces Ca2+ Overload in Ischemic-Reperfused Rat Hearts.

Effects of <i>Leonurine</i> on L-Type Calcium Channel in Rat Ventricular Myocytes

Attenuation of Endoplasmic Reticulum Stress-Related Myocardial Apoptosis by SERCA2a Gene Delivery in Ischemic Heart Disease

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