INVESTIGADORES
VALVERDE Carlos Alfredo
congresos y reuniones científicas
Título:
Reperfusion Causes Cytosolic Calcium Overload Due to Rapid Calcium Release from the Sarcoplasmic Reticulum
Autor/es:
VALVERDE CA; KORNYEYEV D; ESCOBAR AL; MATTIAZZI A
Lugar:
New Orleans, Louisiana, EE.UU.
Reunión:
Congreso; Scientific Sessions 2008; 2008
Institución organizadora:
American Heart Association
Resumen:
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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, which might be
at least partially caused by Ca2+ influx through the reverse NCX
mode, and not just because of the Ca2+ entry through this exchanger,
as has been previously thought