Effect of cardiac A(1) adenosine receptor overexpression on sarcoplasmic reticulum function.
OBJECTIVE
We investigated the effect of A(1) adenosine receptor overexpression, which has been reported to increase myocardial tolerance to ischemia-reperfusion injury, on sarcoplasmic reticulum (SR) Ca(2+) handling.


METHODS
Transgenic mouse hearts (approximately 300-fold A(1) adenosine receptor overexpression) and wild-type mouse hearts were perfused in the Langendorff mode and subjected either to 80 min of aerobic perfusion or to 30 min of aerobic perfusion, 20 min of global ischemia and 30 min of reperfusion. The hearts were then homogenized and used to assay SR oxalate-supported 45Ca(2+) uptake and [3H]-ryanodine binding.


RESULTS
Transgenic hearts showed increased resistance to ischemia-reperfusion, as shown by lower diastolic tension (1.5 +/- 0.2 vs. 2.6 +/- 0.1 g, P<0.05) and higher recovery of developed tension (45 +/- 3 vs. 30 +/- 4% of the baseline, P<0.05) following ischemia-reperfusion. Under baseline conditions, oxalate-supported 45Ca(2+) uptake was lower in transgenic hearts, owing to reduced V(max) (10.6 +/- 2.0 vs. 17.8 +/- 2.7 nmol/min per mg of protein, P<0.05), and the difference was preserved after ischemia-reperfusion (10.0 +/- 1.0 vs. 15.7 +/- 2.5 nmol/min per mg of protein, P<0.05). No significant difference in [3H]-ryanodine binding was observed.


CONCLUSIONS
A(1) adenosine receptor overexpression is associated with a decreased rate of active Ca(2+) transport into the SR. We hypothesize that changes in SR function may cause a depletion of the SR Ca(2+) pool, which might protect from ischemic injury by delaying the development of cytosolic Ca(2+) overload during ischemia.
Zucchi
Riccardo
R
Departimento di Scienze dell'Uomo e dell'Ambiente, University of Pisa, 56126 Pisa, Italy. r.zucchi@med.unipi.it
Cerniway
Rachael J
RJ
Ronca-Testoni
Simonetta
S
Morrison
R Ray
RR
Ronca
Giovanni
G
Matherne
G Paul
GP
D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011485:Protein Binding; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012433:Ryanodine / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D018047:Receptors, Purinergic P1; D012433:Ryanodine; D002118:Calcium