High-conductance, voltage- and calcium-activated potassium channels (BKCa) and store-operated calcium channels (SOCs) are belong to K⁺ channels superfamily and calcium channels superfamily respectively. Since BKCa potassium channels can be activated by calcium ions, we set out to examine whether SOCs are coupled with BKCa and to probe the relationship of BKCa and SOCs. First, we proved that BKCa immunoprecipitated with Orai1, and confocal microscopy showed that BKCa co-localized with Orai1. Next, we mapped that the exact binding sites locate in the 350aa-371aa fragment of the first regulatory domain associated with K⁺ conduction (RCK1) and the 720aa-814aa fragment in the second regulatory domain associated with K⁺ conduction (RCK2) via GST-pull-down assays. Then, we showed, by calcium imaging that BKCa overexpression enhanced endogenous and exogenous store-operated calcium entry (SOCE) and this enhancement could be blocked by Orai1 knockdown. Finally, we proved that SOCE could enhance the activity of BKCa by patch-clamp. From these results we conclude that BKCa can form a positive feedback loop with SOCs, as the Ca²⁺ influx from SOCs can active BKCa, which can hyperpolarize the plasma membrane. In turn, the hyperpolarized membrane will form a higher electric potential difference and give more force, allowing Ca²⁺ influx via SOCs.

高电导，电压和钙激活的钾离子通道（BKCa）和储氢钙离子通道（SOCs）分别属于K ⁺离子通道超家族和钙离子通道超家族。由于BKCa钾离子通道可以被钙离子激活，因此我们着手研究SOC是否与BKCa偶联，并探讨BKCa与SOC的关系。首先，我们证明了BKCa与Orai1发生了免疫沉淀，共聚焦显微镜显示BKCa与Orai1共定位。接下来，我们绘制了确切的结合位点中具有K个相关联的第一调节结构域的350aa-371aa片段定位⁺传导（RCK1）和具有K相关联的第二调节域的720aa-814aa片段⁺通过GST下拉测定法进行传导（RCK2）。然后，我们通过钙成像显示，BKCa过表达增强了内源性和外源性存储钙输入（SOCE），而这种增强可能被Orai1敲低了。最后，我们证明了SOCE可以通过膜片钳增强BKCa的活性。从这些结果可以得出结论，BKCa可以与SOC形成正反馈回路，因为来自SOC的Ca ²⁺流入可以激活BKCa，从而使质膜超极化。反过来，超极化膜将形成更高的电势差并提供更大的作用力，从而允许Ca ²⁺通过SOC流入。