Optogenetic tools enable sophisticated measurements of a voltage-gated sodium channel implicated in pain, as well as high-throughput screening of candidate channel blockers.
Highly temperature-sensitive behavior of voltage-gated potassium channels provides a mechanistic model for how heat-activated TRP channels serve as temperature and pain sensors.
Monica L Fernández-Quintero, Yousra El Ghaleb ... Bernhard E Flucher
Structure modeling, site-directed mutagenesis, and current recordings revealed the mechanism by which stabilization of voltage sensors in the resting and activated states determines the gating properties of the CaV1.1 calcium channel.
Contrary to a generally accepted principle, the pore properties of KCNQ1 channels depend on the states of voltage-sensing domains activation; KCNE1 alters the voltage-sensing domains-pore coupling to modulate KCNQ1 channel properties.
Richard K Hite, Joel A Butterwick, Roderick MacKinnon
Phosphatidic acid influences the gating of voltage-gated K+ channels through a non-specific surface charge mechanism and through a specific interaction between a voltage sensor arginine and the primary phosphate head group on the cytoplasmic membrane leaflet.
Visualization of the real-time conformational transitions of the human voltage-gated proton channel hHv1 provided novel insights into how voltage and pH gradients modify the dynamic behaviors of channel structures to control proton flow across membrane.
Anirban Banerjee, Alice Lee ... Roderick MacKinnon
Charybdotoxin, a toxin produced by scorpions, blocks a K+ channel by binding in a lock-and-key fashion to the mouth of the channel and presenting a lysine amino group, which serves as a K+ mimic in the selectivity filter.
Briana M Bohannon, Alicia de la Cruz ... H Peter Larsson
Polyunsaturated fatty acid analogues show selectivity for different cardiac ion channels, suggesting their potential use for the treatment of different subtypes of Long QT Syndrome.
The HCN1 channel gates thanks to a coupling mechanism involving the reorganization of the interfaces between the voltage-sensor domains and pore helices, subtly shifting the balance between hydrophobic and hydrophilic interactions in a 'domino effect'.