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Electrical nerve stimulation serves an expanding list of clinical applications, but it faces persistent challenges in selectively activating bundled nerve ibers. In this study, we investigated electrochemical modulation with an ion-selective membrane (ISM) and whether it, used together with electrical stimulation, may provide an approach for selective control of peripheral nerves. Guided by theoretical transport modeling and direct concentration measurements, we developed an implantable, multimodal ISM cuf capable of simultaneous electrical stimulation and focused Ca2+ depletion. Acutely implanting it on the sciatic nerve of a rat in vivo, we demonstrated that Ca2+ depletion could increase the sensitivity of the nerve to electrical stimulation. Furthermore, we found evidence that the efect of ion modulation would selectively inluence functional components of the nerve, allowing selective activation by electrical current. Our results raise possibilities for improving functional selectivity of new and existing bioelectronic therapies, such as vagus nerve stimulation. [ABSTRACT FROM AUTHOR]

Abstract Ion selective membrane (ISM) electrodes are widely used for selective ion sensing applications. Recently, new modalities have emerged whose operation involves active electrical polarization of the media, and current theoretical models are unsuitable to predict their behavior beyond near-equilibrium conditions. Here, we apply numerical modeling of physicochemical transport in such systems to study mechanisms of interfacial ion transfer and their role in limiting processes. Importantly, our analysis suggest that membrane-phase complexation (MC) has strong merits as a replacement for interfacial complexation (IC) in theoretical treatments. For our purpose, we have developed a highly detailed model based on Nernst–Planck–Poisson (NPP) with kinetic reactions of first-order. The solutions were derived in terms of logarithmically transformed concentration variables, allowing us to input experimentally determined stability coefficients. A unique process, referred to here as the reaction boundary layer (RBL), is a characteristic of MC, and we found it could have a significant impact on current–voltage (I–V) characteristics and transfer selectivity. Together with other well-known processes such as electrically driven diffusion, the RBL dictates the limits of ISM electrical polarization. Using our model, we demonstrate that operating outside these limits results in ingress of interfering ion species and concurrent loss of transfer selectivity. Highlights • Membrane complexation has strong merits as the intrinsic mechanism of interfacial ion transfer. • A reaction boundary layer effectively produces an intrinsic ISM current limit. • ISM over-limiting processes generally result in loss of transfer selectivity for the primary ion. [ABSTRACT FROM AUTHOR]