Hydrophobic interaction between contiguous residues in the S6 transmembrane segment acts as a stimuli integration node in the BK channel.

ABSTRACT: Large-conductance Ca(2+)- and voltage-activated K(+) channel (BK) open probability is enhanced by depolarization, increasing Ca(2+) concentration, or both. These stimuli activate modular voltage and Ca(2+) sensors that are allosterically coupled to channel gating. Here, we report a point mutation of a phenylalanine (F380A) in the S6 transmembrane helix that, in the absence of internal Ca(2+), profoundly hinders channel opening while showing only minor effects on the voltage sensor active-resting equilibrium. Interpretation of these results using an allosteric model suggests that the F380A mutation greatly increases the free energy difference between open and closed states and uncouples Ca(2+) binding from voltage sensor activation and voltage sensor activation from channel opening. However

SUBMITTER: Carrasquel-Ursulaez W 

PROVIDER: S-EPMC4278184 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature