Postischemic Changes in Cardiac Sarcoplasmic Reticulum Ca2 plus Channels: A Possible Mechanism of Ischemic Preconditioning

• Published in: Circulation research Vol. 76; no. 6; pp. 1049 - 1056
• Main Authors: Zucchi, Riccardo, Ronca-Testoni, Simonetta, Yu, Gongyuan, Galbani, Paola, Ronca, Giovanni, Mariani, Mario
• Format: Journal Article
• Language: English
• Published: American Heart Association, Inc 01.06.1995
• ISSN: 0009-7330; 1524-4571

We investigated the modifications of cardiac ryanodine receptors/sarcoplasmic reticulum Ca plus release channels occurring in ischemic preconditioning.In an isolated rat heart model, the injury produced by 30 minutes of global ischemia was reduced by preexposure to three 3-minute periods of global ischemia (preconditioning ischemia). The protection was still present 120 minutes after preconditioning ischemia but disappeared after 240 minutes. Three 1-minute periods of global ischemia did not provide any protection. In the crude homogenate obtained from ventricular myocardium, the density of [() H]ryanodine binding sites averaged 372 plus minus 18 fmol/mg of protein in the control condition, decreased 5 minutes after preconditioning ischemia (290 plus minus 15 fmol/mg, P less than .01), was still significantly reduced after 120 minutes (298 plus minus 17 fmol/mg, P less than .05), and recovered after 240 minutes (341 plus minus 21 fmol/mg). Three 1-minute periods of ischemia did not produce any change in ryanodine binding. The Kd for ryanodine (1.5 plus minus 0.3 nmol/L) was unchanged in all cases. In parallel experiments, the crude homogenate or a microsomal fraction was passively loaded with Ca, and Ca plus-induced Ca plus release was studied by the quick filtration technique. In both preparations, the rate constant of Ca plus-induced Ca plus release decreased 5 and 120 minutes after preconditioning ischemia (homogenate values19.7 plus minus 1.4 and 18.9 plus minus 0.9 s 1 vs a control value of 25.4 plus minus 1.7 s () 1, P less than .05 in both cases) and recovered after 240 minutes (23.0 plus minus 1.9 s 1). The Ca plus dependence of Ca plus-induced Ca plus release was not affected by preconditioning ischemia. In conclusion, changes in sarcoplasmic reticulum Ca plus-release channels occur after brief ischemia and reperfusion, are closely correlated with the development of myocardial protection versus sustained ischemia, and might play a role in the pathogenesis of ischemic preconditioning.(Circ Res. 1995;76:1049-1056.)