Reperfusion after Ichemia Causes Cytosolic Calcium Overload Due to Rapid Calcium Release from the Sarcoplasmic Reticulum
After a brief ischemic insult, a sustained contractile dysfunction occurs manifested as a sluggish recovery of pump function (myocardial stunning). Substantial evidence supports that myocardial dysfunction is triggered by Ca2+ overload during reperfusion (R). Previous results from different laborato...
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| Autores principales: | , , , |
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| Formato: | Articulo Comunicacion |
| Lenguaje: | Inglés |
| Publicado: |
2009
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/139279 |
| Aporte de: |
| Sumario: | After a brief ischemic insult, a sustained contractile dysfunction occurs manifested as a sluggish recovery of pump function (myocardial stunning). Substantial evidence supports that myocardial dysfunction is triggered by Ca2+ overload during reperfusion (R). Previous results from different laboratories including our own, describe a cascade of events triggered by R that involves the activation of Na+/H+ and Na+/Ca2+ (NCX) exchangers, with enhanced Ca2+ influx. Whether this Ca2+ influx directly produces the increase in cytosolic Ca2+ or this increase occurs as a consequence of sarcoplasmic reticulum (SR) Ca2+ release triggered in turn by the Ca2+ influx, is not known. To address this issue, we performed 12 min of global no-flow ischemia followed by R in the isovolumic Langendorff perfused mouse heart positioned on a Pulsed Local Field Fluorescence microscope and loaded with fluorescent dyes (Rhod-2 or Mag-Fluo-4 to assess cytosolic or SR Ca2+, respectively). The results indicated an initial increase in diastolic Ca2+ during early R that gradually returned to pre-ischemic levels. This increase was associated with a decrease in SR Ca2+ content that recovered within 10 min, as a mirror image of the diastolic Ca2+ profile. Additional experiments in which caffeine pulses (20 mM) were applied, confirmed that SR Ca2+ content was greatly diminished at the onset of R and gradually recovered within 10 min of R. The present findings indicate that the increase in diastolic Ca2+ that occurs upon R is due to a SR Ca2+ release and not just because of the Ca2+ entry through the reverse NCX mode, as has been previously thought. |
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