[Sarcolemmal sodium-calcium exchanger mediated the beneficial effects of myocardial ischemic preconditioning and pharmacological preconditioning].
OBJECTIVE
To investigate the role of sodium-calcium exchanger (NCX) on ischemic preconditioning and pharmacological preconditioning.


METHODS
Cultured rat neonatal cardiomyocytes were randomly divided into 6 groups: (1) ischemia/reperfusion group (9 h ischemia followed by 1 h reperfusion, I/R), (2) ischemic preconditioning group (1.5 h ischemia/1 h reperfusion + I/R), (3) pharmacologic preconditioning group, adenosine (10 micromol/L) pretreated for 1 h + I/R, (4) calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 (0.5 micromol/L for 0.5 h) + ischemic preconditioning group, (5) KN-93 + pharmacologic preconditioning group, (6) control group. The leakage of intracellular lactate dehydrogenase (LDH) in various groups was determined by biochemical autoanalyzer. Semi-quantitative RT-PCR was employed to measure the mRNA levels of sodium-calcium exchanger. Activity of sodium-calcium exchanger (Na(+)-dependent (45)Ca(2+) uptake) was measured by liquid scintillation counting.


RESULTS
(1) Compared to the I/R group, the LDH leakages in both ischemic preconditioning group and pharmacologic preconditioning group were significantly reduced (P < 0.05) while significantly increased in the KN-93 + pharmacologic preconditioning group and the KN-93 + ischemic preconditioning group (P < 0.05). (2) The Na(+)-dependent (45)Ca(2+) uptake was significantly increased in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05). (3) The expression of NCX mRNA in I/R group was also significantly increased (P < 0.05) in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05), CaMKII inhibitor KN-93 significantly abolished these effects in preconditioning group (P < 0.05) and in adenosine pretreated group (P < 0.05).


CONCLUSIONS
NCX mediated the cardioprotective effects of ischemic preconditioning and pharmacological preconditioning in the neonatal cardiomyocytes I/R model.
Zhu
Bao-hua
BH
Department of Cardiology, Yangzhou First People's Hospital, Yangzhou 225001, China. yzbaohua@yahoo.com
Xi
Qun-ying
QY
Liu
Chen
C
Zhang
Neng-feng
NF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D007770:L-Lactate Dehydrogenase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium