Rapid inactivation of depletion-activated calcium current (ICRAC) due to local calcium feedback.
Rapid inactivation of depletion-activated calcium current (ICRAC) due to local calcium feedback.
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DOI：
10.1085/jgp.105.2.209
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发表时间：
1995-02
期刊：
影响因子：
--
通讯作者：
Lewis RS
中科院分区：
文献类型：
--
作者：
Zweifach A;Lewis RS
应用全细胞膜片钳记录和[Ca ~（2+）]i测定技术研究了Jurkat白血病T淋巴细胞Ca ~（2+）释放激活的Ca ~（2+）通道（CRAC）的快速失活。在存在22 mM细胞外Ca 2+的情况下，在超极化脉冲至比-40 mV更负的电位期间，Ca 2+电流以双指数时间过程（时间常数为8-30 ms和50-150 ms）下降。几条证据表明，快速失活过程是钙离子，但不依赖于电压。首先，失活的速度和程度通过增加Ca 2+通过开放通道进入的速率的条件来增强。第二，当Ba 2+作为电荷载体存在时，失活大大减少。第三，通过用BAPTA（12 mM）（一种快速Ca 2+缓冲液）进行细胞内透析减缓失活，但不通过将EGTA（一种较慢的螯合剂）的细胞质浓度从1.2 mM提高到12 mM来减缓失活。在复极化至-12 mV后200 ms内完成从快速失活的恢复。快速失活不受开放CRAC通道或全局[Ca 2 +]i数量变化的影响。这些结果表明，ICRAC的快速失活是由于靠近单个通道的细胞内口的Ca 2+的作用，并且Ca 2+通过一个CRAC通道进入不会影响相邻通道。在存在移动的缓冲液的情况下，Ca 2+扩散的简单模型预测了位于孔的细胞内口3-4 nm处的多个Ca 2+失活位点，与CRAC通道本身的位置一致。
Rapid inactivation of Ca2+ release-activated Ca2+ (CRAC) channels was studied in Jurkat leukemic T lymphocytes using whole-cell patch clamp recording and [Ca2+]i measurement techniques. In the presence of 22 mM extracellular Ca2+, the Ca2+ current declined with a biexponential time course (time constants of 8-30 ms and 50-150 ms) during hyperpolarizing pulses to potentials more negative than -40 mV. Several lines of evidence suggest that the fast inactivation process is Ca2+ but not voltage dependent. First, the speed and extent of inactivation are enhanced by conditions that increase the rate of Ca2+ entry through open channels. Second, inactivation is substantially reduced when Ba2+ is present as the charge carrier. Third, inactivation is slowed by intracellular dialysis with BAPTA (12 mM), a rapid Ca2+ buffer, but not by raising the cytoplasmic concentration of EGTA, a slower chelator, from 1.2 to 12 mM. Recovery from fast inactivation is complete within 200 ms after repolarization to -12 mV. Rapid inactivation is unaffected by changes in the number of open CRAC channels or global [Ca2+]i. These results demonstrate that rapid inactivation of ICRAC results from the action of Ca2+ in close proximity to the intracellular mouths of individual channels, and that Ca2+ entry through one CRAC channel does not affect neighboring channels. A simple model for Ca2+ diffusion in the presence of a mobile buffer predicts multiple Ca2+ inactivation sites situated 3-4 nm from the intracellular mouth of the pore, consistent with a location on the CRAC channel itself.
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影响因子：
64.8
作者：
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通讯作者：
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通讯作者：
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