Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain.
Am J Physiol Cell Physiol. 2013 Jul 15;305(2):C160-72. doi: 10.1152/ajpcell.00016.2013. Epub 2013 Apr 17.
The activity of the plasmalemmal Na(+)/Ca(2+) exchanger (NCX) is highly sensitive to temperature. We took advantage of this fact to explore here the effects of the NCX blocker KB-R7943 (KBR) at 22 and 37°C on the kinetics of Ca(2+) currents (ICa), cytosolic Ca(2+) ([Ca(2+)]c) transients, and catecholamine release from bovine chromaffin cells (BCCs) stimulated with high K(+), caffeine, or histamine. At 22°C, the effects of KBR on those parameters were meager or nil. However, at 37°C whereby the NCX is moving Ca(2+) at a rate fivefold higher than at 22°C, various of the effects of KBR were pronounced, namely: 1) no effects on ICa; 2) reduction of the [Ca(2+)]c transient amplitude and slowing down of its rate of clearance; 3) blockade of the K(+)-elicited quantal release of catecholamine; 4) blockade of burst catecholamine release elicited by K(+); 5) no effect on catecholamine release elicited by short K(+) pulses (1-2 s) and blockade of the responses produced by longer K(+) pulses (3-5 s); and 6) potentiation of secretion elicited by histamine or caffeine. Furthermore, the more selective NCX blocker SEA0400 also potentiated the secretory responses to caffeine. The results suggest that at physiological temperature the NCX substantially contributes to shaping the kinetics of [Ca(2+)]c transients and the exocytotic responses elicited by Ca(2+) entry through Ca(2+) channels as well as by Ca(2+) release from the endoplasmic reticulum.
质膜 Na(+)/Ca(2+) 交换体（NCX）的活性对温度高度敏感。我们利用这一事实，在 22°C 和 37°C 下，探讨了 NCX 阻断剂 KB-R7943（KBR）对高 K(+)、咖啡因或组胺刺激牛嗜铬细胞（BCC）时 Ca(2+) 电流（ICa）、细胞内 Ca(2+)（[Ca(2+)]c）瞬变和儿茶酚胺释放动力学的影响。在 22°C 时，KBR 对这些参数的影响微不足道或没有。然而，在 37°C 时，NCX 以比 22°C 高五倍的速度转运 Ca(2+)，KBR 的各种作用变得明显，即：1）对 ICa 无影响；2）减少 [Ca(2+)]c 瞬变幅度并减缓其清除率；3）阻断 K(+)诱导的儿茶酚胺量子释放；4）阻断 K(+)诱导的爆发性儿茶酚胺释放；5）对 1-2 秒的短 K(+)脉冲引起的儿茶酚胺释放无影响，并阻断 3-5 秒的较长 K(+)脉冲引起的反应；6）增强组胺或咖啡因引起的分泌。此外，更具选择性的 NCX 阻断剂 SEA0400 也增强了咖啡因引起的分泌反应。结果表明，在生理温度下，NCX 对 Ca(2+) 通道介导的 Ca(2+) 内流以及内质网 Ca(2+) 释放引起的 [Ca(2+)]c 瞬变和胞吐反应动力学有重要贡献。
