Dry eye disease is very common worldwide and often resistant to available therapeutics. Verma et al. developed a computational model linking tear production, evaporation, and drainage with ocular surface epithelial transport to predict tear film thickness and osmolality. The model was used to evaluate current therapies for dry eye disease and propose novel cellular targets.

Lorenzo-Ceballos et al. show that long-term inactivation (LTI) of Na_V1.2 channels mediated by A-isoforms of different FGF homologues (FGF11–FGF14) differ both in intrinsic rates of onset and rates of recovery from LTI. Furthermore, FGF’s allosterically mediate slowing of fast inactivation. Specific effects of each FGF-A result in homologue-specific use-dependent changes in Na_V availability.

This study reveals that a KCNE4 polymorphism differentially regulates Kv1.3 activity. This work highlights how the size and charge of a single residue within an anionic cluster critically shape the function of Kv1.3.

Using specific gene subunit knockout mice, Scala et al. show that K_ATP channels formed exclusively of SUR2/Kir6.2 cause delayed fatigue and development of unstimulated force in isolated EDL skeletal muscles, suggesting similar contractile deficits will be present in ABCC9-dependent intellectual disability myopathy syndrome and KCNJ11-dependent neonatal diabetes.

Lukyanenko et al. show that dysferlin’s N-terminal C2 domain, DysfC2A, regulates skeletal muscle Ca²⁺ signaling and membrane repair specifically. DysfC2A does not target triad junctions, whereas the homologous but inactive PKCαC2 domain does. DysfC2A targeted to triad junctions as a PKCαC2 chimera is as active as dysferlin itself, suggesting possible use for dysferlin gene replacement.

Using a combined biophysical and computational approaches, we determined how morphological, intrinsic, and extrinsic factors shape spiking activity in vivo. The computational model was fitted to spiking experimental data, and the variations in the resulting parameters were used to predict the altered spiking activity. Our methodology is likely applicable to other systems and species.

Hussey et al. evaluate the impact of disease-causing mutations in calmodulin on multiple voltage-gated calcium channels. The study demonstrates a disruption of the calcium/calmodulin-dependent regulation Ca_V1.3 and Ca_V2.1 channels by calmodulin variants, expanding the potential molecular targets in the pathogenesis of calmodulinopathies.