SPECIES-DIFFERENCES IN THE ACTIVITY OF THE NA+-CA2+ EXCHANGER IN MAMMALIAN CARDIAC MYOCYTES
SPECIES-DIFFERENCES IN THE ACTIVITY OF THE NA+-CA2+ EXCHANGER IN MAMMALIAN CARDIAC MYOCYTES
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DOI：
10.1113/jphysiol.1995.sp020995
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发表时间：
1995-11-01
影响因子：
5.5
通讯作者：
MORAD, M
中科院分区：
文献类型：
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作者：
SHAM, JSK;HATEM, SN;MORAD, M
1. 在大鼠、豚鼠、仓鼠心室和人心房分离的肌细胞中评估了交换剂活性的物种差异。使用fura-2的荧光测量与全细胞膜片钳技术一起进行，同时记录膜电流和细胞内Ca2+浓度。肌浆网（SR） Ca2+释放是由咖啡因的快速应用或Ca2+电流引起的内Na+-Ca2+交换电流（I-Na-Ca）引起的。I-Na-Ca在仓鼠中最大，在大鼠中最小，在豚鼠和人肌细胞中处于中等水平。咖啡因诱导的交换电流密度之比，相对于Ca2+峰值释放归一化，仓鼠>豚鼠大于等于人大于等于大鼠肌细胞为4:2:15 .5:1。在咖啡因的存在下，Ca2+的去除率主要反映了Na+-Ca2+交换器的Ca2+挤出活性，遵循相同的顺序，仓鼠>豚鼠大于等于人大于等于大鼠。I-Na-Ca和Ca2+瞬态动力学在不同物种之间存在差异。在大鼠肌细胞中，i - na - ca和Ca2+瞬态的动力学非常相似，i - na - ca与细胞内Ca2+浓度成线性比例（[Ca2+](i)）。在仓鼠肌细胞中，I-Na-Ca的时间过程只跟踪Ca2+瞬态的下降阶段，在Ca2+释放过程中，I-Na-Ca具有更快的动力学。这些结果表明，在仓鼠肌细胞Ca2+释放过程中，交换器附近的Ca2+浓度显著高于胞浆。我们得出结论，心肌细胞的交换活性存在显著的物种差异，这是由于交换密度、它们的调节和/或它们在心肌细胞中相对于ryanodine受体的空间分布的差异。
1. Species differences in the activity of the exchanger were evaluated in isolated myocytes from rat, guinea-pig, hamster ventricles and human atria. Fluorescence measurements using fura-2 were carried out in conjunction with the whole-cell patch-clamp technique for simultaneous recording of membrane currents and intracellular Ca2+ concentration.2. Ca2+ release from sarcoplasmic reticulum (SR) induced either by rapid application of caffeine or by Ca2+ current elicited inward Na+-Ca2+ exchange currents (I-Na-Ca). The magnitude of I-Na-Ca was largest in hamster, smallest in rat, with guinea-pig and human myocytes having intermediate values. The ratio of caffeine-induced exchanger current densities, normalized with respect to the peak Ca2+ release, was 4:2:1.5:1 for hamster > guinea-pig greater than or equal to human greater than or equal to rat myocytes.3. The rates of Ca2+ removal in the presence of caffeine, which reflect primarily the Ca2+ extruding activity of the Na+-Ca2+ exchanger, followed the same order of hamster > guinea-pig greater than or equal to human greater than or equal to rat.4. The kinetics of I-Na-Ca vs. Ca2+ transients sr ere different among species. In rat myocytes, the kinetics of the I-Na-Ca and the Ca2+ transients mere similar, with I-Na-Ca linearly proportional to intracellular Ca2+ concentration ([Ca2+](i)). In hamster myocytes, the time course of I-Na-Ca tracked only the declining phase of the Ca2+ transient with I-Na-Ca having faster kinetics during the Ca2+ release. These findings suggest that the Ca2+ concentrations in the vicinity of the exchanger were significantly higher than those of the cytosol during Ca2+ release in hamster myocytes.5. We concluded that there are significant species differences in the exchanger activity of cardiac myocytes, arising from differences in exchanger densities, their modulation and/or their spatial distribution with respect to the ryanodine receptors of cardiac myocytes.