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    ON THE COVER
    The centipede Scolopendra polymorpha is a small venomous animal. Ramu et al. have purified from its venom a small protein that inhibits K+ conduction through the pore of the ATP-sensitive K+ channels naturally present in human pancreatic insulin-secreting cells. Gain-of-function mutations in these channels increase the steady-state macroscopic K+ current across the plasmalemma and thereby cause permanent neonatal diabetes mellitus.
    Photo credit: Charles Kristensen.
    See page 969.

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ISSN 0022-1295
EISSN 1540-7748

Research News

JGP study examines claudin-15 ion selectivity and permeation.

Essay

JGP 100th Anniversary

Ashcroft reflects on the support and generosity of colleagues who have helped shape her scientific endeavor.

Commentary

Allard appraises recent studies investigating the pathological mechanism of hypokalemic periodic paralysis mutations.

Jones et al. provide commentary on the intricate crosstalk between ion transporters that goes awry in long QT arrhythmia.

Lam and Chesler highlight the recent discovery of a G protein–coupled receptor involved in detecting mechanical shear stress.

Milestone in Physiology

A voltage change across a membrane protein moves charges or dipoles producing a gating current that is an electrical expression of a conformational change.

Review

Falzone et al. interpret the mechanisms underlying the activity of TMEM16 family members from recent structural and functional work.

Article

Members of the claudin family form tight junctions between adjacent epithelial and endothelial cells. Samanta et al. build an atomic model of claudin-15 using molecular dynamics simulations and conclude that four claudin-15 molecules each contribute an aspartic acid residue to form a selectivity filter.

Mutations in ATP-sensitive K+ channels can cause permanent neonatal diabetes mellitus, and patients with some mutations become practically insensitive to the common antidiabetic drug sulphonylurea. Ramu et al. identify a 54-residue protein (SpTx-1) that inhibits human wild-type and sulphonylurea-insensitive mutant KATP channels with a Kd of 15 nM.

The conductance of the strong inward rectifier K+ channel depends on the “square root” of the extracellular K+ concentration. The present study shows that this physiologically important phenomenon is caused by a channel blockade by extracellular Na+, which is competitive with extracellular K+.

Neuronal Na+ channels contribute to catecholaminergic polymorphic ventricular tachycardia in the heart, but their role in other types of arrhythmias is unknown. Koleske et al. show that they contribute to early and delayed afterdepolarizations common to long QT, catecholaminergic polymorphic ventricular tachycardia, and overlap phenotypes.

Communication

Volume-regulated anion channels (VRACs) comprise the essential LRRC8A subunit plus one or more LRRC8 paralogs. By engineering chimeras that form homomeric channels, Yamada and Strange show that the intracellular and first extracellular loops of LRRC8 are essential for VRAC structure and function.

Activation of voltage-gated channels results from the outward movement of arginine residues on the S4 segments. Infield et al. use in vivo nonsense suppression to replace Shaker's S4 arginine residues with citrulline and reveal that a positive charge is required on R4 for voltage-dependent deactivation.

Voltage-gated ion channels are subject to posttranslational modification, including glycosylation. Lopez-Rodriguez and Holmgren show that, in Shaker KV channels, deglycosylation influences voltage sensing and open–closed transitions but not binding of ligands to the protein.

Methods and Approaches

The mitochondrial calcium uniporter is a Ca2+ channel that has been hard to characterize electrophysiologically. Tsai and Tsai establish a method that permits efficient electrophysiological recordings of the human uniporter in Xenopus oocytes and demonstrate characteristic uniporter behaviour.

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