Provides high-resolution mapping of the S4-S5 linker movement in voltage-gated K+ channels, offering insights into the mechanisms of electrical excitability in the heart and nervous system.
Offers mechanistic views of K+ channel gating in excitability; leaves open translation to human arrhythmias or therapies.
Significance Excitability in heart and nervous system is based on sensing and propagation of the membrane potential by voltage-gated ion channels. Despite the increasing availability of high-resolution structures of voltage-gated ion channels, key questions about their dynamics remain elusive. Here we followed the movements of the gating machinery on the cytosolic surface of the Shaker K V channel by introducing a fluorescent noncanonical amino acid at different positions along the linker between voltage sensor and pore. We can thus map the movement of each position and reconstruct the dynamics of the gating machinery during activation and inactivation. Considering that the Shaker channel serves as a model system, the mechanisms are likely conserved among those K V channels containing a sizeable S4–S5 linker.
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Kalstrup et al. (2018) studied this question.
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