Linker-Gating Ring Complex as Passive Spring and Ca²⁺-Dependent Machine for a Voltage- and Ca²⁺-Activated Potassium Channel

Abstract

Ion channels are proteins that control the flux of ions across cell membranes by opening and closing (gating) their pores. It has been proposed that channels gated by internal agonists have an intracellular gating ring that extracts free energy from agonist binding to open the gates using linkers that directly connect the gating ring to the gates. Here we find for a voltage- and Ca²⁺-activated K⁺ (BK) channel that shortening the linkers increases channel activity and lengthening the linkers decreases channel activity, both in the presence and absence of intracellular Ca²⁺. These observations are consistent with a mechanical model in which the linker-gating ring complex forms a passive spring that applies force to the gates in the absence of Ca²⁺ to modulate the voltage-dependent gating. Adding Ca²⁺ then changes the force to further activate the channel. Both the passive and Ca²⁺-induced forces contribute to the gating of the channel.