Hydrophobic interactions between the HA helix and S4-S5 linker modulate apparent Ca²⁺ sensitivity of SK2 channels.

ABSTRACT:

Aim

Small-conductance Ca²⁺ -activated potassium (SK) channels are activated exclusively by increases in intracellular Ca²⁺ that binds to calmodulin constitutively associated with the channel. Wild-type SK2 channels are activated by Ca²⁺ with an EC₅₀ value of ~0.3 μmol/L. Here, we investigate hydrophobic interactions between the HA helix and the S4-S5 linker as a major determinant of channel apparent Ca²⁺ sensitivity.

Methods

Site-directed mutagenesis, electrophysiological recordings and molecular dynamic (MD) simulations were utilized.

Results

Mutations that decrease hydrophobicity at the HA-S4-S5 interface lead to Ca²⁺ hyposensitivity of SK2 channels. Mutations that increase hydrophobicity result in hy

SUBMITTER: Nam YW 

PROVIDER: S-EPMC7736289 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature