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New JGP study explains how auxiliary proteins relieve polyamine block of AMPARs.

Commentary

Aalkjær and Nielsen discuss new data revealing the basis of acid–base transport in t-tubules of skeletal muscle.

Milestone in Physiology

Armstrong and Hollingworth discuss inactivation in the light of modern structural data from K and Na channels.

Viewpoint

Chiu and colleagues review the primary evidence for divergent activation mechanisms and unitary properties of Pannexin 1 channels.

Article

The bacterial pyridine nucleotide uptake family of transporters mediates the uptake of B-type vitamins, but their transport mechanism is unknown. Jaehme et al. show that the PnuT thiamine transporter utilizes a facilitated diffusion mechanism and supports metabolic trapping of phosphorylated thiamine.

Sodium–calcium exchangers contribute to the generation of intracellular Ca2+ signals in numerous physiological processes. Shlosman et al. determine the ion stoichiometry of the only sodium–calcium exchanger of known atomic structure, revealing its functional similarity to mammalian exchangers.

Polyamine block of AMPA-type ionotropic glutamate receptors is attenuated by auxiliary proteins stargazin and cornichon-3. Brown et al. show that relief from block is due to enhanced blocker permeation and present a modified model of permeant channel block to account for their experimental findings.

Ca2+-dependent facilitation is a positive feedback mechanism that regulates Cav2.1 P/Q-type channels but not closely related Cav2.2 N-type channels. Thomas et al. identify the molecular determinants that distinguish the ability of Cav2.1 and Cav2.2 to undergo Ca2+-dependent facilitation.

The regulation of pH across the t-system membrane of skeletal muscle fibers is poorly understood. Using a sealed tubule preparation, Launikonis et al. reveal Na+/H+ exchange activity and characterize the properties of the diffusional and NHE proton fluxes across the t-system.

Malignant hyperthermia can result from mutations in the ryanodine receptor that favor anesthetic-induced Ca2+ release. Zullo et al. find that membrane potential modulates the effect of the volatile anesthetic halothane on skeletal muscle ryanodine receptors possessing the Y524S mutation.

The swimbladder muscle of the Pacific midshipman fish contracts up to 360,000 times in an hour while generating mating calls. Using experimental measurements and computational modeling, Nelson et al. reveal the Ca2+ handling that permits these superfast muscle fibers to sustain high-frequency calling.

Coronary blood flows through a complex vasculature that is regulated by a number of physiological mechanisms, including myogenic, shear regulation, and metabolic control. Namani et al. describe a fully integrative and anatomically correct model that accurately predicts experimental observations.

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