Newest Articles
Epilepsy-causing mutation in S4 of KCNQ3KCNQ2 and KCNQ3 are subunits of the M channel, which regulates neuronal excitability. Using voltage clamp fluorometry, Barro-Soria reveals that the R230C mutation in KCNQ3, which causes hyperexcitability, shifts the voltage dependence of the open/closed transition to negative potentials.
Myofilament meeting 2018The first of two special issues dedicated to contractile systems highlights an emerging consensus that regulatory mechanisms involve thick and thin filaments.
Cardiac recovery with reexpression of cMyBP-CKnockdown of cardiac myosin binding protein C (cMyBP-C), which is the cause of many cases of hypertrophic cardiomyopathy in humans, results in left ventricular dilation, cardiac hypertrophy, and impaired ventricular function, but it is unclear whether these effects can be reversed. Using the Tet-Off system, Giles et al. show that these phenotypes can be induced and reversed with reexpression of cMyBP-C on the null background.
Metformin ameliorates diastolic dysfunctionHeart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by increased diastolic stiffness, for which effective therapies are lacking. Slater et al. show that metformin lowers titin-based passive stiffness in an HFpEF mouse model and may therefore be of therapeutic benefit.
Hanging on by the helixNavarro et al discuss new work using the gating-modifier toxin GxTx to investigate the molecular mechanism of Kv2.1 channel gating.
State-dependent binding of cAMP to spHCN channelsMammalian hyperpolarization-activated cyclic-nucleotide–modulated (HCN) channels bind cAMP preferably in the open state. Using sea urchin HCN channels, Idikuda et al. reveal less cAMP binding to the closed state and further reduced binding to the inactivated state and thus demonstrate intricate communication between the gate and ligand-binding domain.
RyR2 modulation by phosphorylation at S2030Phosphorylation is thought to play a role in modulation of the ryanodine receptor 2 channel. Using a S2030A knock-in mouse model, Potenza et al. reveal that phosphorylation of RyR2-S2030 mediates channel regulation during the β-adrenergic response.
Destabilization of relaxation in hERG channelsThe human ether-à-go-go–related gene (hERG) encodes a delayed rectifier K+ channel with slow deactivation gating. Shi et al. find that acidic residues on S3 contribute to slow deactivation kinetics by stabilizing the relaxed state of the voltage sensor, which can be mitigated by extracellular protons.
Control of Cx26 gating by cytosolic domainsThe N14K mutation in the N-terminal domain of connexin26 produces gain-of-function hemichannels. Valdez Capuccino et al. reveal that the mutation disrupts intersubunit interactions between the N terminus and the second transmembrane domain–cytoplasmic loop transition.
Titin compliance reduces length-dependent troponin regulationIncreases in sarcomere length cause enhanced force generation in cardiomyocytes by an unknown mechanism. Li et al. reveal that titin-based passive tension contributes to length-dependent activation of myofilaments and that tightly bound myosin–actin cross-bridges are associated with this effect.
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Current Issue
February 4, 2019
Volume 151, No. 2
