Issues

New simulations explain how several types of drugs block sodium channels.

Chavan et al. highlight work showing that a monobody can inhibit a fluoride channel using a mechanism similar to that of a scorpion toxin blocker of potassium channels.

Csanády discusses a new study that provides insight into the unique conductance properties of the CFTR chloride channel.

Bretag traces the history of glass microelectrodes back to the 17th century.

A timely review of the structural basis of Ca²⁺-activated K⁺ channel modulation by regulator of conduction of K⁺ (RCK) domains

Peinado Allina et al. measure rod responses in living mice across a wide range of flash strengths and find that responses are much faster in vivo than ex vivo, though the biochemical mechanisms underlying the kinetics appear to be the same in both cases. Although RGS9 overexpression sped recovery from bright flashes, faster rod recovery did not improve the temporal resolution of scotopic vision.

Insect photoreceptors utilize two light-activated channels, TRP and TRPL, in their phototransduction cascades, but the American cockroach Periplaneta americana depends strongly on TRPL. Saari et al. show that TRPL generates high-gain and high-noise phototransduction suitable for dim light vision.

A number of different drugs block sodium channels, but their mechanism of block is unclear. Tikhonov and Zhorov combine homology modeling with ligand docking and propose a pharmacophore for sodium channel blockers involving cationic and aromatic moieties.

The role of T-type calcium channels in animals without nervous systems is unknown. Smith et al. characterize TCa_v3 from Trichoplax adhaerens, finding expression in neurosecretory-like cells and preference for Ca²⁺ over Na⁺ via strong extracellular Ca²⁺ block, despite low selectivity for Ca²⁺ in the pore.

Fibronectin domain monobodies bind to both sides of Fluc Fl⁻ channels in a negatively cooperative way, but crystal structures show two monobodies binding simultaneously. Turman and Stockbridge resolve this contradiction by showing that monobodies block channel pores by means of a negatively charged loop.

A conserved glutamic acid residue is thought to occupy three different conformations in the transport pathway of CLC H⁺/Cl⁻ exchangers. Vien et al. provide functional evidence that the most central of these three positions is adopted by CLC-ec1 during transport and is stabilized by hydrogen bonds.