Premium
Glutamate protects against Ca 2+ paradox‐induced injury and inhibits calpain activity in isolated rat hearts
Author(s) -
Zhang JianYing,
Kong LingHeng,
Lai Dong,
Jin ZhenXiao,
Gu XiaoMing,
Zhou JingJun
Publication year - 2016
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12605
Subject(s) - glutamate receptor , calpain , chemistry , medicine , calcium , endocrinology , biochemistry , pharmacology , biology , enzyme , receptor
Summary This study determined the effects of glutamate on the Ca 2+ paradoxical heart, which is a model for Ca 2+ overload‐induced injury during myocardial ischaemia and reperfusion, and evaluated its effect on a known mediator of injury, calpain. An isolated rat heart was retrogradely perfused in a Langendorff apparatus. Ca 2+ paradox was elicited via perfusion with a Ca 2+ ‐free Krebs‐Henseleit ( KH ) solution for 3 minutes followed by Ca 2+ ‐containing normal KH solution for 30 minutes. The Ca 2+ paradoxical heart exhibited almost no viable tissue on triphenyltetrazolium chloride staining and markedly increased LDH release, caspase‐3 activity, cytosolic cytochrome c content, and apoptotic index. These hearts also displayed significantly increased LVEDP and a disappearance of LVDP . Glutamate (5 and 20 mmol/L) significantly alleviated Ca 2+ paradox‐induced injury. In contrast, 20 mmol/L mannitol had no effect on Ca 2+ paradox. Ca 2+ paradox significantly increased the extent of the translocation of μ‐calpain to the sarcolemmal membrane and the proteolysis of α‐fodrin, which suggests calpain activation. Glutamate also blocked these effects. A non‐selective inhibitor of glutamate transporters, dl ‐TBOA (10 μmol/L), had no effect on control hearts, but it reversed glutamate‐induced cardioprotection and reduction in calpain activity. Glutamate treatment significantly increased intracellular glutamate content in the Ca 2+ paradoxical heart, which was also blocked by dl ‐TBOA. We conclude that glutamate protects the heart against Ca 2+ overload‐induced injury via glutamate transporters, and the inhibition of calpain activity is involved in this process.