Calcium sensitivity of BK-type K_Ca channels determined by a separable domain

High conductance, Ca²⁺-activated (BK-type) K⁺ channels from mouse (mSlo) and Drosophila (dSlo) differ in their functional properties but share a conserved core resembling voltage-gated K⁺ channels and a tail appended to the core by a nonconserved linker. We have found that the channel subunit is physically divisible into these two conserved domains and that the core determines such properties as channel open time, conductance, and, probably, voltage dependence, whereas the tail determines apparent Ca²⁺ sensitivity. Both domains are required for function. We demonstrated the different roles of the core and tail by taking advantage of the functional differences between mSlo and dSlo. Heterologous pairing of cores and tails from mSlo and dSlo showed that single-channel properties were always characteristic of the core species, but that apparent Ca²⁺ sensitivity was adjusted up or down depending on the species of the tail. Thus, the tail is implicated in the Ca²⁺-sensing role of BK channels.