JGP study reveals that the calcium sensitivity of thick filament structure in skeletal muscle is greater than that of force, offering new insights into the mechanisms of thick filament activation.
Studies using isolated myosin and troponin–tropomyosin from either heart or skeletal muscle show new features of contractile regulation.
Thick filament structure in skeletal muscle is more sensitive to calcium than isometric force, with a higher cooperativity. A novel thick filament structure in which myosin motors take up a longer axial periodicity is formed at partial calcium activation.
Using a recently developed multisite ion model, Liu et al. conducted molecular dynamics simulations to study the Ca2+ binding and permeation in TRPV channels. The ion binding strength and number of binding sites within the selectivity filter are found to be key factors determining the permeation patterns and probably ion selectivity.
Hancock et al. expand their previously developed electrochemical model of pacemaking in lymphatic muscle cells to encompass situations where both the electrical oscillator and the biochemical oscillator are simultaneously active. This model allows new biological findings to be emulated.
IP3R1 underlies diastolic ANO1 activation and pressure-dependent chronotropy in lymphatic collecting vessels
Pressure-dependent lymphatic pacemaking is regulated by the Ca2+-activated Cl− channel, Anoctamin1. Zawieja et al. show that IP3R1-mediated Ca2+ release is the primary Ca2+ source driving Anoctamin1 activation during diastole to regulate pacemaking and contributes to lymphatic vessel tone.
Benndorf and Schulz present a strategy to analyze the functionality of dimeric through pentameric ligand-gated ion channels by combining subunit concatenation, mutagenesis, and extensive global fit strategies with intimately coupled Markov models.
Structural basis for severe pain caused by mutations in the voltage sensors of sodium channel NaV1.7
Mutations in the voltage-gated sodium channel NaV1.7 cause the chronic pain syndrome, inherited erythromelalgia. Structures of bacterial sodium channel NaVAb with these mutations revealed changes that would enhance the outward movement of the gating charges and lead to hyperexcitability underlying chronic pain.
Ishii et al. analyze the microheating-induced sliding movements of reconstituted thin filaments in an in vitro motility assay. They find that the temperature dependence of thin filament sliding is complementarily regulated by myosin and tropomyosin–troponin within the body temperature range.
Methods and Approaches
Murciano et al. present an assay to investigate PIEZO1 channels by combining planar patch clamp with mechanical stimulation. This technique will enable the high-throughput characterization of PIEZO1 channels for screening purposes.