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THE CRYSTAL STRUCTURE OF A VOLTAGE-GATED SODIUM CHANNEL
TLDR
This crystal structure of a voltage-gated Na+ channel from Arcobacter butzleri (NavAb) captured in a closed-pore conformation with four activated voltage sensors provides the template for understanding electrical signalling in excitable cells and the actions of drugs used for pain, epilepsy and cardiac arrhythmia at the atomic level. Expand
Molecular determinants of state-dependent block of Na+ channels by local anesthetics.
TLDR
The results define the location of the local anesthetic receptor site in the pore of the Na+ channel and identify molecular determinants of the state-dependent binding of local anesthetics. Expand
Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy
TLDR
The results indicate that reduced sodium currents in GABAergic inhibitory interneurons in Scn1a+/− heterozygotes may cause the hyperexcitability that leads to epilepsy in patients with SMEI. Expand
Voltage-gated ion channels and gating modifier toxins.
TLDR
Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent neurotoxins, which has now been modeled at the atomic level for a beta-scorpion toxin. Expand
Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.
TLDR
F1764 and Y1771 are common molecular determinants of state-dependent binding of diverse drugs including lidocaine, phenytoin, flecainide, and quinidine, suggesting that these drugs interact with a common receptor site. Expand
A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation.
TLDR
It is proposed that the hydrophobic cluster of Ile-1488, Phe-1489, and Met-1490 serves as a hydrophilic latch that stabilizes the inactivated state in a hinged-lid mechanism of Na(+)-channel inactivation. Expand
Crystal structure of a voltage-gated sodium channel in two potentially inactivated states
TLDR
Crystallographic snapshots of the wild-type NaVAb channel from Arcobacter butzleri captured in two potentially inactivated states provide new insights intoNaV channel gating and novel avenues to drug development and therapy for a range of debilitating NaV channelopathies. Expand
Autoinhibitory control of the CaV1.2 channel by its proteolytically processed distal C‐terminal domain
TLDR
The results provide the first functional characterization of this autoinhibitory complex, which may be a major form of the CaV1 family Ca2+ channels in cardiac and skeletal muscle cells, and reveal a unique ion channel regulatory mechanism in which proteolytic processing produces a more effective autoinhibitor of CaV 1.2 channel function. Expand
Modulation of Ca2+ channels by G-protein βγ subunits
TLDR
For the top panel of Fig. Id, GTP-yS is also included in the intracellular solution as stated in the figure legend, and not GDP- yS as indicated on the figure itself. Expand
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