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A novel Hv1 inhibitor reveals a new mechanism of inhibition of a voltage-sensing domain
Zhao and colleagues use the Hv1 channel to study drugs that modulate channel activity by binding to the voltage-sensing do...
HIFs: New arginine mimic inhibitors of the Hv1 channel with improved VSD–ligand interactions
Zhao et al. leverage the analysis of local conformational changes in a mutant Hv1 channel to inform the design of new inhi...
L-type channel inactivation balances the increased peak calcium current due to absence of Rad in cardiomyocytes
Ahern et al. show that the absence of Rad increases peak L-type calcium influx independently of β-adrenergic receptor sign...
Loss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation
Sewanan et al. studied a mutation to cardiac tropomyosin that causes hypertrophic cardiomyopathy. Computational models, in...
Conformations of voltage-sensing domain III differentially define Na V channel closed- and open-state inactivation
Angsutararux et al. propose that the voltage-sensing domains of repeats III and IV of NaV channels regulate state-dependen...
State-dependent inhibition of BK channels by the opioid agonist loperamide
Vouga et al. show that the opioid receptor agonist loperamide is an inhibitor of large-conductance Ca2+-activated K+ (BK) ...
Widening the scope of constriction
JGP modeling study suggests that selectivity filter constriction is a plausible mechanism for C-type inactivation of the S...
Norfluoxetine inhibits TREK-2 K2P channels by multiple mechanisms including state-independent effects on the selectivity filter gate
Proks et al. show that the antidepressant norfluoxetine affects the behavior of TREK-2 two-pore domain K+ channels by regu...
Mutation of a conserved glutamine residue does not abolish desensitization of acid-sensing ion channel 1
Rook et al. assess how mutations in acid-sensing ion channel 1 (ASIC1) affect channel desensitization. They establish that...
Cooperative binding ensures the obligatory melibiose/Na + cotransport in MelB
Hariharan and Guan find that binding of either melibiose or Na+ to their transporter, MelB, may favor MelB open states, wh...
Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake
Smith et al. use a novel technique for direct measurement of solute transport from cerebrospinal fluid to brain interstiti...
ENaC and ROMK channels in the connecting tubule regulate renal K + secretion
Yang et al. study changes in the activity of the kidney ENaC and ROMK channels in response to variations in K+ levels in t...
Unraveling the mysteries of the titin–N2A signalosome
The sarcomeric titin springs and accessory proteins modulate muscle force and mechanical signaling at the N2A signalosome.
Cardiac mechanical efficiency is preserved in primary cardiac hypertrophy despite impaired mechanical function
Han et al. study the effect of primary cardiac hypertrophy on cardiac mechano-energetics. Using isolated cardiac tissues, ...
A TREK inhibitor takes multiple tracks
Single-channel recordings reveal that norfluoxetine inhibits the two-pore domain K+ channel TREK-2 by a complex array of m...
Zinc binding alters the conformational dynamics and drives the transport cycle of the cation diffusion facilitator YiiP
Lopez-Redondo et al. use cryo-EM and molecular dynamics to evaluate the effects of Zn2+ binding on the conformation and dy...
Intercalated disk nanoscale structure regulates cardiac conduction
Moise et al. develop a finite element model of the intercalated disk (ID) that takes into account the nanoscale structure....
Cardiac MyBP-C phosphorylation regulates the Frank–Starling relationship in murine hearts
Cardiac myosin-binding protein C (cMyBP-C) is thought to regulate cardiac muscle and heart contraction. Hanft et al. show ...
cMyBPC phosphorylation modulates the effect of omecamtiv mecarbil on myocardial force generation
Mamidi et al. investigate the effect of cardiac myosin-binding protein C (cMyBPC) phosphorylation on the response to omeca...
Novel insights into sarcomere regulatory systems control of cardiac thin filament activation
This review focuses on thin filament regulatory mechanisms with emphasis on cardiac-specific mechanisms in the three-state...
The N2A region of titin has a unique structural configuration
Stronczek et al. analyze the structure of the titin-N2A poly-Ig segment, a key signaling element in the sarcomere. They re...
Contraction–relaxation coupling is unaltered by exercise training and infarction in isolated canine myocardium
Fazlollahi et al. show that contraction and relaxation remain tightly coupled in intact canine myocardium after exercise t...
Impact of regulatory light chain mutation K104E on the ATPase and motor properties of cardiac myosin
Rasicci et al. investigate the mechanochemical properties of distinct isoforms of cardiac myosin carrying the K104E regula...
Mavacamten has a differential impact on force generation in myofibrils from rabbit psoas and human cardiac muscle
Scellini et al. show that mavacamten, a preclinical inhibitor of sarcomeric myosins, has a fast and reversible mechanical ...
Cardiomyopathic mutations in essential light chain reveal mechanisms regulating the super relaxed state of myosin
Using mutations associated with cardiomyopathy, Sitbon et al. study the transition between the super relaxed state of myos...
Titin–N2A: More than a signaling node?
Stronczek et al. investigate the structure of titin–N2A and how it affects the binding of signaling proteins.
Why make a strong muscle weaker?
Iorga and Kraft discuss a recent investigation on force inhibition by mavacamten in ventricular and skeletal myofibrils.
Caldesmon ablation in mice causes umbilical herniation and alters contractility of fetal urinary bladder smooth muscle
Contractility of smooth muscle is of vital importance. Pütz et al. reveal that the actin filament–linked protein caldesmon...