1.A.1.3.1
Large conductance, voltage- and Ca²⁺-activated K⁺ (BK or Slo) channel. Four pairs of RCK1 and RICK2 domains form the Ca²⁺-sensing apparatus known as the "gating ring" in Big Potassium (BK) channel proteins (Savalli et al., 2012). Gating of BK channels does not seem to require a physical gate. Instead, changes in the pore shape and surface hydrophobicity in the Ca²⁺-free state allow the channel to readily undergo hydrophobic dewetting transitions, giving rise to a large free energy barrier for K⁺ permeation (Jia et al. 2018).  Voltage-dependent dynamics of the BK channel cytosolic gating ring are coupled to the membrane-embedded voltage sensor (Miranda et al. 2018). Slo channels are targets for insecticides and antiparasitic drugs. Raisch et al. 2021 reported structures of Drosophila Slo in the Ca²⁺-bound and Ca²⁺-free forms and in complex with the fungal neurotoxin verruculogen and the anthelmintic drug emodepside. The architecture and gating mechanism of Slo channels are conserved, but potential insect-specific binding pockets are present. Verruculogen inhibits K⁺ transport by blocking the Ca²⁺-induced activation signal and precludes K⁺ from entering the selectivity filter while emodepside decreases the conductance by suboptimal K⁺ coordination and uncouples ion gating from Ca²⁺ and voltage sensing (Raisch et al. 2021). In neurosecretion, allosteric communication between voltage sensors and Ca²⁺ binding in BK channels is crucially involved in damping excitatory stimuli. Carrasquel-Ursulaez et al. 2022 demonstrated that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. The energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD).