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Fluorescence in situ hybridization showing a nuclear aggregate of expanded CUG repeat RNA in cardiac ventricular tissue from an LC15 transgenic mouse using a 3’ Texas Red-tagged CAG8-repeat 2-O-methyl oligoribonucleotide probe (red). The nucleus was stained with diamidino-2-phenylindole (blue). The nuclear foci of expanded CUG repeat RNA in cardiomyocytes from LC15 mice are similar to those observed in patients with myotonic dystrophy type 1. Image © Tylock et al., 2020. See http://doi.org/10.1085/jgp.201912450.
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Bohannon et al. show that polyunsaturated fatty acids (PUFAs) vary in their ability to activate cardiac IKs potassium channels depending on the pKa of the PUFA head group, allowing PUFAs to be tuned to treat long QT syndrome mutants with different disease severity.
Mammalian isoforms of mitochondrial VDAC have unique functional roles in vivo, but they all share similar β-barrel pore structures. Queralt-Martín et al. provide the first mechanistic insights into VDAC’s isoform-specific function by showing that VDAC3 exhibits unique properties when interacting with cytosolic proteins α-synuclein and tubulin.
Neuronal ASIC channels mediate excitatory sodium currents in response to extracellular acidification. Lynagh et al. reveal the essential roles of pore-lining glutamates in ion conduction and selectivity for ASIC1a- and ASIC2a-containing channels.
Biophysical mechanisms for QRS- and QTc-interval prolongation in mice with cardiac expression of expanded CUG-repeat RNA
The expression of expanded CUG-repeat RNAs in myotonic dystrophy type 1 patients is associated with cardiac electrophysiological defects and an elevated risk of sudden cardiac death. Tylock et al. reveal that expression of these RNAs in the murine heart results in prolonged QRS and corrected QT-intervals due to alterations in sodium and potassium channel activity.
An interaction between the III-IV linker and CTD in NaV1.5 confers regulation of inactivation by CaM and FHF
The auxiliary proteins CaM and FHF bind to the C-terminal domain of voltage-gated sodium channels to limit the persistent inward currents associated with cardiac arrhythmias. Gade et al. reveal that CaM and FHF exert their effects by stabilizing an interaction between the channel’s C-terminal domain and III-IV linker region.