Computational study suggests that π-bulges play an integral role in the gating mechanisms of Cav channels, governing the binding of enantiomeric DHP.
Myosin expression and contractile function are altered by replating stem cell–derived cardiomyocytes
Osten et al. describe rapid changes in myosin heavy chain isoform expression, contractile function, and calcium transients after enzymatic detachment and replating of human stem cell–derived cardiomyocytes (CMs). These changes may alter mechanosensation and need to be considered when replating CMs in the context of functional measurements.
Hu et al. demonstrate that, independent of other countercurrents, TRIC-A and TRIC-B differentially modulate RyR2 gating. Results also suggest that TRIC-A and TRIC-B are permeable to both K+ and Cl−, thus enabling them to provide adaptable countercurrents for many cell types.
ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle
This study examined how structural microdomains comprising the Ca2+-activated Cl− channel encoded by Tmem16a or Anoctamin-1 (ANO1) interact with voltage-gated Ca2+ channel CaV1.2 in the plasma membrane and how Ca2+ release from IP3 receptors in the sarcoplasmic reticulum drive intracellular Ca2+ waves and force production of pulmonary artery smooth muscle cells in response to the vasoconstrictor agonist serotonin.
Cooperative mechanisms underlie differences in myocardial contractile dynamics between large and small mammals
The Fitzsimons lab examines the activation dependence of contractile kinetics in mouse and swine hearts. Their findings demonstrate that the cooperative mechanisms underlying contraction differ in the hearts of small and large mammals and yield insights into normal heart function.
We show that isoproterenol applied to rat ventricular myocytes produced symmetrical increases in the size of ryanodine receptor clusters, a decrease in fragmentation, and the coalescence of smaller clusters. Additionally, receptors were found in irregularly arranged arrays resembling those seen by electron tomography.
Disease-associated KCNMA1 variants decrease circadian clock robustness in channelopathy mouse models
KCNMA1 regulates circadian rhythm in animals, and mutations in this potassium channel are associated with human neuromotor disease. Dinsdale et al. evaluated circadian clock function in three mouse models harboring KCNMA1 mutations associated with human channelopathies and found clock-controlled behavioral deficits without primary rhythm ablation.
Wells et al. show that a transmural conduction gradient that exists in rat ventricular slices is abolished in settings of increased pericardial adiposity, with slowed epicardial conduction strongly correlating with an increase in cardiomyocyte lipid content.
Mechanisms of dihydropyridine agonists and antagonists in view of cryo-EM structures of calcium and sodium channels
Computational models based on different cryo-EM structures of ligand-bound calcium and sodium channels suggest that dihydropyridine antagonists stabilize entirely α-helical conformation of the pore-lining helix S6IV, whereas agonists promote channel opening by stabilizing π-bulged helix S6IV.