AIMS: Transient receptor potential melastatin 2 (TRPM2) highly expressed in 
immunocytes is a Ca(2+)-permeable non-selective cation channel activated by 
oxidative stress. Myocardial ischaemia/reperfusion (I/R) injury is characterized 
by acute inflammation associated with the augmentation of oxidative stress. We 
hypothesized that TRPM2 is implicated in the exacerbation of myocardial I/R 
injury.
METHODS AND RESULTS: Wild-type (Trpm2(+/+)) and Trpm2 knockout (Trpm2(-/-)) mice 
were subjected to ligation of the left main coronary artery followed by 
reperfusion. Myocardial infarction following I/R, but not ischaemia alone, was 
reduced more in Trpm2(-/-)mice than in Trpm2(+/+) mice and cardiac contractile 
functions were also improved in Trpm2(-/-)mice. TRPM2 was highly expressed in 
the polymorphonuclear leucocytes (PMNs) rather than in the heart. The number of 
neutrophils and myeloperoxidase (MPO) activity in the reperfused area following 
ischaemia was lowered in Trpm2(-/-) mice. When Trpm2(+)(/+) or Trpm2(-/-) PMNs 
were administered to the Trpm2(-/-) heart ex vivo through the perfusate or in 
vivo by iv injection, Trpm2(+)(/+) PMNs produced enlargement of the infarct 
size. Following in vitro regional I/R, a pharmacological inhibitor of TRPM2 
reduced the infarct size. The combination of H(2)O(2) and leukotriene B(4) 
(LTB(4)) increased intracellular Ca(2+) concentration and their adhesion to 
endothelial cells in Trpm2(+)(/+) but not in Trpm2(-/-)PMNs.
CONCLUSION: These findings indicate that neutrophil TRPM2 is implicated in the 
exacerbation of myocardial reperfusion injury. Accumulation of neutrophils in 
the reperfused area mediated by TRPM2 activation is likely to play a crucial 
role in myocardial I/R injury.