Single Channel Recordings Reveal Differential [beta]2 Subunit Modulations Between Mammalian and Drosophila BK.sub.Ca Channels

Large-conductance Ca.sup.2+ - and voltage-activated potassium (BK) channels are widely expressed in tissues. As a voltage and calcium sensor, BK channels play significant roles in regulating the action potential frequency, neurotransmitter release, and smooth muscle contraction. After associating with the auxiliary [beta]2 subunit, mammalian BK([beta]2) channels (mouse or human Slo1/[beta]2) exhibit enhanced activation and complete inactivation. However, how the [beta]2 subunit modulates the Drosophila Slo1 channel remains elusive. In this study, by comparing the different functional effects on heterogeneous BK([beta]2) channel, we found that Drosophila Slo1/[beta]2 channel exhibits "paralyzed"-like and incomplete inactivation as well as slow activation. Further, we determined three different modulations between mammalian and Drosophila BK([beta]2) channels: 1) dSlo1/[beta]2 doesn't have complete inactivation. 2) [beta]2(K33,R34,K35) delays the dSlo1/[DELTA]3-[beta]2 channel activation. 3) dSlo1/[beta]2 channel has enhanced pre-inactivation than mSlo1/[beta]2 channel. The results in our study provide insights into the different modulations of [beta]2 subunit between mammalian and Drosophila Slo1/[beta]2 channels and structural basis underlie the activation and pre-inactivation of other BK([beta]) complexes.