The ability to reliably and safely communicate chronically with small diameter (100–300 µm) autonomic nerves could have a significant impact in fundamental biomedical research and clinical applications. However, this ability has remained elusive with existing neural interface technologies. Here we show a new chronic nerve interface using highly flexible materials with axon-like dimensions. The interface was implemented with carbon nanotube (CNT) yarn electrodes to chronically record neural activity from two separate autonomic nerves: the glossopharyngeal and vagus nerves. The recorded neural signals maintain a high signal-to-noise ratio (>10 dB) in chronic implant models. We further demonstrate the ability to process the neural activity to detect hypoxic and gastric extension events from the glossopharyngeal and vagus nerves, respectively. These results establish a novel, chronic platform neural interfacing technique with the autonomic nervous system and demonstrate the possibility of regulating internal organ function, leading to new bioelectronic therapies and patient health monitoring.

Mutations in voltage-gated sodium channels are linked to several channelopathies leading to a wide variety of diseases including cardiac arrhythmias, epilepsy and myotonia. We previously demonstrated that Na1.5 trafficking-deficient mutant channels could lead to a dominant-negative effect by impairing trafficking of the wild-type (WT) channel. We also reported that voltage-gated sodium channels associate as dimers with coupled gating properties. Here, we hypothesized that the dominant-negative effect of mutant sodium channels could also occur through coupled gating. This was tested using cell surface biotinylation and single-channel recordings to measure the gating probability and coupled gating of the dimers. Co-expression of Na1.5-L325R with WT channels led to a dominant-negative effect as reflected by a 75% reduction in current density. Surprisingly, cell surface biotinylation showed that Na1.5-L325R mutant is capable of trafficking, with 40% of Na1.5-L325R reaching the cell surface when expressed alone. Importantly, even though a dominant-negative effect on the sodium current is observed when WT and Na1.5-L325R are expressed together, the total NaV channel cell surface expression was not significantly altered compared to WT alone. Thus, the trafficking deficiency could not explain the 75% decrease in INa. Interestingly, single-channel recordings showed that Na1.5-L325R exerted a dominant-negative effect on the WT at the gating level. Both coupled gating and gating probability of the WT:L325R dimers were drastically impaired. We conclude that dominant-negative suppression exerted by Na1.5 mutants can also be caused by impairing the WT gating probability, a mechanism resulting from the dimerization and coupled gating of voltage-gated sodium channel α-subunits.

Inspired by the cell membrane surface as well as the ocular tissue, a novel and clinically applicable antifouling silicone hydrogel contact lens material was developed. The unique chemical and biological features on the surface on a silicone hydrogel base substrate were achieved by a cross-linked polymer layer composed of 2-methacryloyloxyethyl phosphorylcholine (MPC), which was considered important for optimal on-eye performance. The effects of the polymer layer on adsorption of biomolecules, such as lipid and proteins, and adhesion of cells and bacteria were evaluated and compared with several conventional silicone hydrogel contact lens materials. The MPC polymer layer provided significant resistance to lipid deposition as visually demonstrated by the three-dimensional confocal images of whole contact lenses. Also, fibroblast cell adhesion was decreased to a 1% level compared with that on the conventional silicone hydrogel contact lenses. The movement of the cells on the surface of the MPC polymer-modified lens material was greater compared with other silicone hydrogel contact lenses indicating that lubrication of the contact lenses on ocular tissue might be improved. The superior hydrophilic nature of the MPC polymer layer provides improved surface properties compared to the underlying silicone hydrogel base substrate.

Nav1.5, encoded by the gene SCN5A, is the predominant voltage-gated sodium channel expressed in the heart. It initiates the cardiac action potential and thus is crucial for normal heart rhythm and function. Dysfunctions in Nav1.5 have been involved in multiple congenital or acquired cardiac pathological conditions such as Brugada syndrome (BrS), Long QT Syndrome Type 3, and heart failure (HF), all of which can lead to sudden cardiac death (SCD) – one of the leading causes of death worldwide. Our lab has previously reported that Nav1.5 forms dimer channels with coupled gating. We also found that Nav1.5 BrS mutants can exert a dominant-negative (DN) effect and impair the function of wildtype (WT) channels through coupled-gating with the WT. It was previously reported that reduction in cardiac sodium currents (INa), observed in HF, could be due to the increased expression of an SCN5A splice variant – E28D, which results in a truncated sodium channel (Nav1.5-G1642X). In this study, we hypothesized that this SCN5A splice variant leads to INa reduction in HF through biophysical coupling with the WT. We showed that Nav1.5-G1642X is a non-functional channel but can interact with the WT, resulting in a DN effect on the WT channel. We found that both WT and the truncated channel Nav1.5-G1642X traffic at the cell surface, suggesting biophysical coupling. Indeed, we found that the DN effect can be abolished by difopein, an inhibitor of the biophysical coupling. Interestingly, the sodium channel polymorphism H558R, which has beneficial effect in HF patients, could also block the DN effect. In summary, the HF-associated splice variant Nav1.5-G1642X suppresses sodium currents in heart failure patients through a mechanism involving coupled-gating with the wildtype sodium channel.