Mapping the molecular motions of 5-HT serotonin-gated channel by voltage-clamp fluorometry.

The serotonin-gated ion channel (5-HTR) mediates excitatory neuronal communication in the gut and the brain. It is the target for setrons, a class of competitive antagonists widely used as antiemetics, and is involved in several neurological diseases. Cryo-electron microscopy (cryo-EM) of the 5-HTR in complex with serotonin or setrons revealed that the protein has access to a wide conformational landscape.

Illumination of a progressive allosteric mechanism mediating the glycine receptor activation.

Pentameric ligand-gated ion channel mediate signal transduction at chemical synapses by transiting between resting and open states upon neurotransmitter binding. Here, we investigate the gating mechanism of the glycine receptor fluorescently labeled at the extracellular-transmembrane interface by voltage-clamp fluorometry (VCF). Fluorescence reports a glycine-elicited conformational change that precedes pore opening.

Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway.

Glycine receptors (GlyRs) are ligand-gated ion channels mediating signal transduction at chemical synapses. Since the early patch-clamp electrophysiology studies, the details of the ion permeation mechanism have remained elusive. Here, we combine molecular dynamics simulations of a zebrafish GlyR-α1 model devoid of the intracellular domain with mutagenesis and single-channel electrophysiology of the full-length human GlyR-α1.

Using Symmetrical Organic Cation Solutions to Study P2X7 Ion Permeation.

P2X7 receptors are ATP-gated ion channels permeable to metal cations, such as Na, K, and Ca. They also exhibit permeability to various large molecular weight species, reaching up to 900 Da, in a process known as macropore formation, which is a unique functional hallmark across the P2X family. While well-documented in a range of different cell types, the molecular mechanism underlying this phenomenon is poorly understood, and has been clouded through the use of electrophysiological methodology prone to artifacts as a result of significant changes in ionic concentrations in asymmetric conditions.