Shen et al. show that mutating countercharge residues in Ciona intestinalis voltage-sensing phosphatase result in the formation of a continuous water path through the voltage-sensing domain and the generation of omega currents. Their work reveals a novel role for voltage-sensor countercharges.

Enamel-forming cells direct the transport of calcium out of the cell to help mineralize the enamel crystals. Sodium/calcium exchangers are proteins that efficiently extrude calcium. In enamel cells, NCKX proteins dominate this function explaining why patients with defective NCKX4 have enamel defects.

VPC01091.4 and AAL-149 are FTY720 analogs that inhibit TRPM7 without targeting S1P receptors and exert multimodal anti-inflammatory effects in vivo. In a mouse endotoxemia model, VPC01091.4 reduces inflammation and disease severity without impacting blood lymphocyte counts.

Mutations in the voltage-gated sodium channel Na_V1.7 cause the chronic pain syndrome, inherited erythromelalgia. Structures of bacterial sodium channel Na_VAb with these mutations revealed changes that would enhance the outward movement of the gating charges and lead to hyperexcitability underlying chronic pain.

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.

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.

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.