Khoo and Pless examine new work that provides mechanistic insight into the role of the intrinsic ligand in KCNH ion channels.
Milestone in Physiology
Ríos relates the history of Ca2+-induced Ca2+ release and how its contribution to skeletal muscle physiology was determined.
Hwang et al. integrate new structural insights with prior functional studies to reveal the functional anatomy of CFTR chloride channels.
RPE65 is a retinoid isomerase essential for rod function, but its contribution to cone vision is enigmatic. Using selective RPE65 inhibitors, Kiser et al. demonstrate that cone function depends only partially on continuous RPE65 activity, providing support for cone-specific regeneration mechanisms.
In addition to recycling vesicles, synaptic endocytosis restores release site competence after exocytosis. Wen et al. show that endocytosis is essential for subsequent fusion but not docking of vesicles at photoreceptor ribbon synapses and for maintaining release at modest frequencies.
Stac proteins associate with the critical domain for excitation–contraction coupling in the II–III loop of CaV1.1
In skeletal muscle, excitation–contraction coupling between CaV1.1 and RyR1 depends on the presence of a critical domain (residues 720–764/5) within the cytoplasmic II–III loop of CaV1.1. Polster et al. identify the adaptor protein Stac3 as a direct interaction partner of the critical domain.
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.
Methods and Approaches
Ion channel proteins can be in vitro translated into nanoscale lipid bilayers known as nanodiscs. Winterstein et al. show that they can subsequently insert into planar bilayers, providing a rapid and contamination-free method for functional characterization.