Cover picture: Giant unilamellar liposomes (∼1–30 μm) are generated by application of an alternating voltage to a solvent-free lipid film, a process called electroformation. These vesicles were used for reconstitution and direct electrophysiological characterization of a prokaryotic sodium–calcium exchanger with an approach utilizing solid supported membranes (see Methods and Approaches by Barthmes et al., 485–496).
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Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels
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.
The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1
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
Electrophysiological characterization of the archaeal transporter NCX_Mj using solid supported membrane technology
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.
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.