Functional coupling between BKCa and SOC channels.

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.