April 2017 | Volume 149, No. 4

Research Articles

• Research Articles

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    Bright flash response recovery of mammalian rods in vivo is rate limited by RGS9

    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.

    Gabriel Peinado Allina, Christopher Fortenbach, Franklin Naarendorp, Owen P. Gross, Edward N. Pugh, Marie E. Burns
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    Distinct roles of light-activated channels TRP and TRPL in photoreceptors of Periplaneta americana

    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.

    Paulus Saari, Andrew S. French, Päivi H. Torkkeli, Hongxia Liu, Esa-Ville Immonen, Roman V. Frolov
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    Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants

    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.

    Denis B. Tikhonov, Boris S. Zhorov
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    Evolutionary insights into T-type Ca²⁺ channel structure, function, and ion selectivity from the Trichoplax adhaerens homologue

    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.

    Carolyn L. Smith, Salsabil Abdallah, Yuen Yan Wong, Phuong Le, Alicia N. Harracksingh, Liana Artinian, Arianna N. Tamvacakis, Vincent Rehder, Thomas S. Reese, Adriano Senatore
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    Mechanism of single- and double-sided inhibition of dual topology fluoride channels by synthetic monobodies

    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.

    Daniel L. Turman, Randy B. Stockbridge

• Communication

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    Probing the conformation of a conserved glutamic acid within the Cl⁻ pathway of a CLC H⁺/Cl⁻ exchanger

    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.

    Malvin Vien, Daniel Basilio, Lilia Leisle, Alessio Accardi