Single Channel Recordings Reveal Differential Beta 2 Subunit Modulations Between Mammalian And Drosophila Bkca(Beta 2) Channels

Large-conductance Ca2+- 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 Sio1 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.