Membrane stretch and cytoplasmic Ca2+ independently modulate stretch-activated BK channel activity

Large conductance Ca2+-activated K+ (BK) channels are responsible for changes in chemical and physical signals such as Ca2+, Mg2+ and membrane potentials. Previously, we reported that a BK channel cloned from chick heart (SAKCaC) is activated by membrane stretch. Molecular cloning and subsequent functional characterization of SAKCaC have shown that both the membrane stretch and intracellular Ca2+ signal allosterically regulate the channel activity via the linker of the gating ring complex. Here we investigate how these two gating principles interact with each other. We found that stretch force activated SAKCaC in the absence of cytoplasmic Ca2+. Lack of Ca2+ bowl (a calcium binding motif) in SAKCaC diminished the Ca2+-dependent activation, but the mechanosensitivity of channel was intact. We also found that the abrogation of STREX (a proposed mechanosensing apparatus) in SAKCaC abolished the mechanosensitivity without altering the Ca2+ sensitivity of channels. These observations indicate that membrane stretch and intracellular Ca2+ could independently modulate SAKCaC activity.