Instituto de Investigaciones Cardiológicas, Universidad de Buenos Aires-CONICET, Argentina.
Acta Physiol (Oxf). 2010 Jul 1;199(3):293-304. doi: 10.1111/j.1748-1716.2010.02094.x. Epub 2010 Feb 2.
Cardiac basal metabolism upon extracellular calcium removal and its relationship with intracellular sodium and calcium homeostasis was evaluated.
A mechano-calorimetric technique was used that allowed the simultaneous and continuous measurement of both heat rate and resting pressure in arterially perfused quiescent adult rat hearts. Using pharmacological tools, the possible underlying mechanisms related to sodium and calcium movements were investigated.
Resting heat rate (expressed in mW g(-1)(dry wt)) increased upon calcium withdrawal (+4.4 +/- 0.2). This response was: (1) unaffected by the presence of tetrodotoxin (+4.3 +/- 0.6), (2) fully blocked by both, the decrease in extracellular sodium concentration and the increase in extracellular magnesium concentration, (3) partially blocked by the presence of either nifedipine (+2.8 +/- 0.4), KB-R7943 (KBR; +2.5 +/- 0.2), clonazepam (CLO; +3.1 +/- 0.3) or EGTA (+1.9 +/- 0.3). The steady heat rate under Ca(2+)-free conditions was partially reduced by the addition of Ru360 (-1.1 +/- 0.2) but not CLO in the presence of EGTA, KBR or Ru360.
Energy expenditure for resting state maintenance upon calcium withdrawal depends on the intracellular rise in both sodium and calcium. Our data are consistent with a mitochondrial Ca(2+) cycling, not detectable under normal calcium diastolic levels. The experimental condition here analysed, partially simulates findings reported under certain pathological situations including heart failure in which mildly increased levels of both diastolic sodium and calcium have also been found. Therefore, under such pathological conditions, hearts should distract chemical energy to fuel processes associated with sodium and calcium handling, making more expensive the maintenance of their functions.
评估细胞外钙去除后心脏基础代谢以及其与细胞内钠和钙稳态的关系。
采用机械量热技术，同时连续测量动脉灌注静止成年大鼠心脏的心率和静息压。使用药理学工具研究与钠和钙运动相关的潜在机制。
静息心率（以 mW/g(-1)(干重)表示）在钙缺失时增加（+4.4 +/- 0.2）。这种反应是：(1) 不受河豚毒素存在的影响（+4.3 +/- 0.6），(2) 完全被降低细胞外钠浓度和增加细胞外镁浓度阻断，(3) 部分被硝苯地平（nifedipine，nif；+2.8 +/- 0.4）、KB-R7943（KBR；+2.5 +/- 0.2）、氯硝西泮（clonazepam，CLO；+3.1 +/- 0.3）或 EGTA 阻断。在无钙条件下的稳定心率部分被 Ru360 降低（-1.1 +/- 0.2），但在 EGTA、KBR 或 Ru360 存在下，添加 CLO 不会降低。
钙缺失后维持静息状态的能量消耗取决于细胞内钠和钙的增加。我们的数据与线粒体钙循环一致，在正常钙舒张水平下无法检测到。这里分析的实验条件部分模拟了在某些病理情况下发现的结果，包括心力衰竭，其中也发现了轻度增加的舒张钠和钙水平。因此，在这种病理条件下，心脏应该分散化学能量来为与钠和钙处理相关的过程提供燃料，从而使维持其功能的成本更高。
