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CaV1.1 is a slowly activating voltage-gated Ca2+ channel that exists in two splice variants with different voltage sensitivities. By making chimeras of these variants, Tuluc et al. show that activation kinetics and voltage dependence are controlled by distinct molecular mechanisms in the voltage-sensing domains of repeats I and IV, respectively.

Electrophiles produced during oxidative stress trigger pain responses by reacting with TRPA1 ion channels on sensory nerves. Bahia et al. show that residue C621 on TRPA1 has remarkable reactivity with electrophiles—more than cellular antioxidants—and is crucial for this sensory response.

Extracellular ATP activates receptors such as P2X ligand-gated ion channels, but it also chelates divalent cations. Nörenberg et al. find that experimental conditions designed to measure P2X7 activity also activate TRPM7 channels, by relieving inhibition by extracellular divalent cations, in HEK293 and rat C6 glioma cells.

Methods and Approaches

NCX_Mj is a sodium–calcium exchanger from the archaebacterium Methanococcus jannaschii, whose crystal structure has been solved. Barthmes et al. use solid supported membrane–based electrophysiology to characterize NCX_Mj and reveal its functional similarity to eukaryotic isoforms.

Communication

TREK channels, which are gated open by a wide range of stimuli, exist in at least two conformations known as “up” and “down.” McClenaghan et al. show that the channel can be open in both of these conformations and that gating is primarily achieved by the channel’s selectivity filter.

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