Utp Myocardial Cytoprotection And Calcium Transport

AIM: To study the protective effects of UTP on damaged cardiomyocytes and its mechanism. METHODS: Cultured cardiomyocytes and acute isolated cardiomycytes were used: (1) To mimick oxidational myocardium damage-induced by H2O2, and evaluate the protective effects of UTP on it with electron microscopy and biological indexes such as LDH, MDA, and SOD. (2) To observe the effects of UTP on the [Ca2+]i of cardiomyocytes with laser confocal microscopy. (3) To observe the effects of UTP on L-type calcium current with whole-cell patch clamp techniques. RESULTS: (1) UTP could significantly alleviate the cardiomyocytes damages induced by H2O2. UTP could reduce LDH release from cultured cardiomyocytes and the content of MDA, increasing the SOD activity in cardiomyocytes at 1 and lOjimol-L"1. According to the electron microscopy, the internal mitochondrial membrane formed cristae and was closely aligned with the external membrane. The intermembrane gap and intracristae space had a constant width in the control group. As a result of H2O2 damage, electron microscopy showed fused inner and outer membranes and affected cristae of some mitochondria. The damages induced by H2O2 is relatively mild in UTP lumol-L"1 group, and the damages in UTP lOumol-I/'group can be significantly alleviated; (2) Laser confocal microscopy showed that UTP at lumol-L"1 markedly increased the [Ca2+]i in systole with no notable effect on the [Ca^Ji in diastole. At lOumol-L'1 UTP increased [Ca2+]i insystole greatly and decreased the [Ca2+]i in diastole. These effects were attenuated by adding calcium antagonist, lacidipine (O.Sumol-L"1) in Hank's solution or replacing the extracellular Hank's solution with D-Hank's solution, showing that L-calcium channels were involed in the effects of UTP on [Ca2+]i metabolism; (3) UTP at 1 and 10 umol-L'1 significantly increased L-type calcium current in cardiomyocytes while not changing calcium channel activating properties. CONCLUSION: UTP can prevent cardiomyocytes from damages induced by oxidation, enhancing the calcium metabolism, i.e. increases both positive contraction and relaxation of myocardium. It shows useful clinic significance to protect myocardium and promote its function.