Steady-state and dynamic properties of cardiac sodium-calcium exchange. Secondary modulation by cytoplasmic calcium and ATP.
Steady-state and dynamic properties of cardiac sodium-calcium exchange. Secondary modulation by cytoplasmic calcium and ATP.
复制标题
心脏钠钙交换的稳态和动态特性。细胞质钙和ATP的次要调节。
DOI：
10.1085/jgp.100.6.933
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发表时间：
1992-12
期刊：
影响因子：
--
通讯作者：
Matsuoka S
中科院分区：
文献类型：
--
作者：
Hilgemann DW;Collins A;Matsuoka S
在离体豚鼠心肌细胞巨膜膜片上，观察了心肌钠钙交换电流对胞浆钙和MgATP变化的动态反应。二次依赖性的交换电流对细胞质钙占两种机制：（a）钠依赖性失活过程，称为I1调制，本身是强烈调制的细胞质钙。细胞质钙的增加加速了从I1失活状态的恢复，并且计算出的进入I1失活的速率减慢。(b)第二个调节过程，称为I2调节，不依赖于钠。与I1调节一样，在细胞质钙缺乏的情况下，进入I2失活需要数秒。从I2失活的恢复是钙依赖性的转变，并且在微摩尔游离钙存在下是快速的（< 200 ms）。I1和I2调节可以被视为线性的、独立的过程，以解释观察到的大多数交换调节模式：（a）当细胞质钙在高细胞质钠的存在下增加或减少时，外向交换电流分别在多秒的时间尺度上打开或关闭。(b)当在细胞质钙缺乏的情况下应用钠时，没有外向电流被激活。然而，当细胞质钙与钠一起应用时，在溶液转换时间内激活全部外向电流。(c)在应用胞质钠时获得的峰值外向电流的钙依赖性从稳态交换电流的钙依赖性向较低浓度偏移约1个对数单位。(d)随着细胞质钙减少到亚微摩尔范围，细胞质钙减少时外向电流衰减的时间过程变得更快。(e)在几乎所有的条件下，在应用细胞质钠和/或细胞质钙的去除过程中的电流衰减的时间过程是很好的拟合单指数。MgATP对这两种调制过程都有明显的影响。与细胞质钙的作用类似，MgATP减慢进入I1失活并加速从失活中恢复。MgATP还可使细胞质钙离子去除后外向交换电流的衰减减慢2-10倍，表明对I2失活的影响。最后，细胞质钙对钠-钙交换电流的影响被重建在I1和I2调制过程作为独立反应的模拟中。
Dynamic responses of cardiac sodium-calcium exchange current to changes of cytoplasmic calcium and MgATP were monitored and analyzed in giant membrane patches excised from guinea pig myocytes. Secondary dependencies of exchange current on cytoplasmic calcium are accounted for in terms of two mechanisms: (a) The sodium-dependent inactivation process, termed I1 modulation, is itself strongly modulated by cytoplasmic calcium. Recovery from the I1 inactivated state is accelerated by increasing cytoplasmic calcium, and the calculated rate of entrance into I1 inactivation is slowed. (b) A second modulation process, termed I2 modulation, is not sodium dependent. As with I1 modulation, the entrance into I2 inactivation takes place over seconds in the absence of cytoplasmic calcium. The recovery from I2 inactivation is a calcium-dependent transition and is rapid (< 200 ms) in the presence of micromolar free calcium. I1 and I2 modulation can be treated as linear, independent processes to account for most exchange modulation patterns observed: (a) When cytoplasmic calcium is increased or decreased in the presence of high cytoplasmic sodium, outward exchange current turns on or off, respectively, on a time scale of multiple seconds. (b) When sodium is applied in the absence of cytoplasmic calcium, no outward current is activated. However, the full outward current is activated within solution switch time when cytoplasmic calcium is applied together with sodium. (c) The calcium dependence of peak outward current attained upon application of cytoplasmic sodium is shifted by approximately 1 log unit to lower concentrations from the calcium dependence of steady-state exchange current. (d) The time course of outward current decay upon decreasing cytoplasmic calcium becomes more rapid as calcium is reduced into the submicromolar range. (e) Under nearly all conditions, the time courses of current decay during application of cytoplasmic sodium and/or removal of cytoplasmic calcium are well fit by single exponentials. Both of the modulation processes are evidently affected by MgATP. Similar to the effects of cytoplasmic calcium, MgATP slows the entrance into I1 inactivation and accelerates the recovery from inactivation. MgATP additionally slows the decay of outward exchange current upon removal of cytoplasmic calcium by 2-10-fold, indicative of an effect on I2 inactivation. Finally, the effects of cytoplasmic calcium on sodium- calcium exchange current are reconstructed in simulations of the I1 and I2 modulation processes as independent reactions.