Konieczny Vera, Tovey Stephen C, Mataragka Stefania, Prole David L, Taylor Colin W
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Cell Rep. 2017 Jan 17;18(3):711-722. doi: 10.1016/j.celrep.2016.12.058.
Inositol 1,4,5-trisphosphate (IP) stimulates Ca release from the endoplasmic reticulum (ER), and the response is potentiated by 3',5'-cyclic AMP (cAMP). We investigated this interaction in HEK293 cells using carbachol and parathyroid hormone (PTH) to stimulate formation of IP and cAMP, respectively. PTH alone had no effect on the cytosolic Ca concentration, but it potentiated the Ca signals evoked by carbachol. Surprisingly, however, the intracellular Ca stores that respond to carbachol alone could be both emptied and refilled without affecting the subsequent response to PTH. We provide evidence that PTH unmasks high-affinity IP receptors within a discrete Ca store. We conclude that Ca stores within the ER that dynamically exchange Ca with the cytosol maintain a functional independence that allows one store to be released by carbachol and another to be released by carbachol with PTH. Compartmentalization of ER Ca stores adds versatility to IP-evoked Ca signals.
肌醇1,4,5-三磷酸（IP）可刺激内质网（ER）释放钙离子，并且3',5'-环磷酸腺苷（cAMP）可增强该反应。我们在人胚肾293（HEK293）细胞中分别使用卡巴胆碱和甲状旁腺激素（PTH）来刺激IP和cAMP的形成，从而研究这种相互作用。单独使用PTH对胞质钙离子浓度没有影响，但它能增强由卡巴胆碱诱发的钙离子信号。然而，令人惊讶的是，单独对卡巴胆碱作出反应的细胞内钙离子储存库既能排空又能重新填充，而不会影响随后对PTH的反应。我们提供的证据表明，PTH可使离散的钙离子储存库内的高亲和力IP受体暴露出来。我们得出结论，在内质网中与胞质动态交换钙离子的钙离子储存库保持着功能上的独立性，使得一个储存库可被卡巴胆碱释放，而另一个储存库可在PTH存在的情况下被卡巴胆碱释放。内质网钙离子储存库的区室化增加了IP诱发的钙离子信号的多样性。
