Different agonists activate the muscle AChR with different efficacies. Mukhtasimova and Sine show that oxidative cross-linking of proximal residues alters the ability of some agonists but not others to open the AChR channel. The findings show that, in opening the channel, agonists with differing efficacy elicit distinct structural changes.

Mutations in connexin 26 hemichannels that cause syndromic deafness have a gain-of-function phenotype that is poorly understood. García et al. show that one such mutation impairs fast and slow gating in these hemichannels because of an interaction between the N terminus and intracellular loop.

KCNH potassium channels possess an intrinsic ligand in their cyclic nucleotide-binding homology domain, located at the N- and C-terminal domain interface. Dai et al. show that this intrinsic ligand regulates voltage-dependent potentiation via a rearrangement between the ligand and its binding site.