Cryo-EM structure of the open high conductance Ca ²⁺-activated K ⁺ channel

Abstract

The Ca ²⁺-activated K ⁺ channel, Slo1, has an unusually large conductance and contains a voltage sensor and multiple chemical sensors. Dual activation by voltage and Ca ²⁺ renders Slo1 central to numerous cellular processes that couple electrical signaling to Ca ²⁺-mediated events such as muscle contraction and neuronal excitability. Here we present the cryo-electron microscopy structure of a full-length Slo1 channel from Aplysia californica in the presence of Ca ²⁺ and Mg ²⁺ at a resolution of 3.5 Å. The channel adopts an open conformation. Its voltage sensor domain adopts a non-domain-swapped attachment to the pore and contacts the cytoplasmic Ca ²⁺-binding domain from a neighboring subunit. Unique structural features of the Slo1 voltage sensor suggest that Slo1 likely employs a voltage sensing mechanism quite distinct from known voltage-dependent ion channels. The structure reveals the molecular details of three distinct divalent cation-binding sites identified through electrophysiological studies of mutant Slo1 channels.