Stress-Axis Regulated Exon (STREX) in the C terminus of BK_Ca channels is responsible for the stretch sensitivity

We previously reported that SAK_CA, a stretch-activated, large-conductance, calcium- and voltage-activated potassium (BK_Ca) channel is present in chick embryonic heart. Here, we cloned SAK_CA and identified that Stress-Axis Regulated Exon (STREX) is responsible for the stretch sensitivity. Single patch-clamp recordings from CHO cells transfected with the cloned SAK_CA showed stretch sensitivity, whereas deletion of the STREX insert diminished the stretch sensitivity of the channel. Sequence analysis revealed that the ERA _672-674 sequence of the STREX is indispensable for channel stretch sensitivity and single amino acid substitution from Ala674 to Thr674 completely eliminated the stretch sensitivity. Co-expression of chick STREX-EGFP and SAK_CA in CHO cells, induced a strong GFP signal in the cell membrane and inhibited the stretch sensitivity significantly. These results suggest that SAK_CA senses membrane tension through an interaction between STREX and submembranous components.