6 research outputs found
Cardioplegia at subnormothermia facilitates rapid functional resuscitation of hearts preserved in SOMAH for transplants
Development of an estimation system based on the relationship between plant genetic resource images and environmental information for the collection point
Resting Membrane Potential Regulates Na+–Ca2+ Exchange-Mediated Ca2+ Overload during Hypoxia–Reoxygenation in Rat Ventricular Myocytes
In the heart, reperfusion following an ischaemic episode can result in a marked increase in [Ca2+]i and cause myocyte dysfunction and death. Although the Na+–Ca2+ exchanger has been implicated in this response, the ionic mechanisms that are responsible have not been identified. In this study, the hypothesis that the diastolic membrane potential can influence Na+–Ca2+ exchange and Ca2+ homeostasis during chemically induced hypoxia–reoxygenation has been tested using right ventricular myocytes isolated from adult rat hearts. Superfusion with selected [K+]o of 0.5, 2.5, 5, 7, 10 and 15 mm yielded the following resting membrane potentials: −27.6 ± 1.63 mV, −102.2 ± 1.89, −86.5 ± 1.03, −80.1 ± 1.25, −73.6 ± 1.02 and −66.4 ± 1.03, respectively. In a second set of experiments myocytes were subjected to chemically induced hypoxia–reoxygenation at these different [K+]o, while [Ca2+]i was monitored using fura-2. These results demonstrated that after chemically induced hypoxia–reoxygenation had caused a marked increase in [Ca2+]i, hyperpolarization of myocytes with 2.5 mm [K+]o significantly reduced [Ca2+]i (7.5 ± 0.32 vs. 16.9 ± 0.55 %); while depolarization (with either 0.5 or 15 mm [K+]o) significantly increased [Ca2+]i (31.8 ± 3.21 and 20.8 ± 0.36 vs. 16.9 ± 0.55 %, respectively). As expected, at depolarized membrane potentials myocyte hypercontracture and death increased in parallel with Ca2+ overload. The involvement of the Na+–Ca2+ exchanger in Ca2+ homeostasis was evaluated using the Na+–Ca2+ exchanger inhibitor KB-R7943. During reoxygenation KB-R7943 (5 μm) almost completely prevented the increase in [Ca2+]i both in control conditions (in 5 mm [K+]o: 2.2 ± 0.40 vs. 10.8 ± 0.14 %) and in depolarized myocytes (in 15 mm [K+]o: −2.1 ± 0.51 vs. 11.3 ± 0.05 %). These findings demonstrate that the resting membrane potential of ventricular myocytes is a critical determinant of [Ca2+]i during hypoxia–reoxygenation. This appears to be due mainly to an effect of diastolic membrane potential on the Na+–Ca2+ exchanger, since at depolarized potentials this exchanger mechanism operates in the reverse mode, causing a significant Ca2+ influx