Electroceuticals: emerging applications beyond the nervous system and excitable tissues.

Electroceuticals have evolved beyond devices manipulating neuronal signaling for symptomatic treatment, becoming more precise and disease modulating and expanding beyond the nervous system. These advancements promise transformative applications in arthritis, cancer treatment, tissue regeneration, and more. Here, we discuss these recent advances and offer insights for future research.

Phenylalanine in the pore of the Erwinia ligand-gated ion channel modulates picrotoxinin potency but not receptor function.

The Erwinia ligand-gated ion channel (ELIC) is a bacterial homologue of eukaryotic Cys-loop ligand-gated ion channels. This protein has the potential to be a useful model for Cys-loop receptors but is unusual in that it has an aromatic residue (Phe) facing into the pore, leading to some predictions that this protein is incapable of ion flux. Subsequent studies have shown this is not the case, so here we probe the role of this residue by examining the function of the ELIC in cases in which the Phe has been substituted with a range of alternative amino acids, expressed in Xenopus oocytes and functionally examined. Most of the mutations have little effect on the GABA EC50, but the potency of the weak pore-blocking antagonist picrotoxinin at F16'A-, F16'D-, F16'S-, and F16'T-containing receptors was increased to levels comparable with those of Cys-loop receptors, suggesting that this antagonist can enter the pore only when residue 16' is small. T6'S has no effect on picrotoxinin potency when expressed alone but abolishes the increased potency when combined with F16'S, indicating that the inhibitor binds at position 6', as in Cys-loop receptors, if it can enter the pore. Overall, the data support the proposal that the ELIC pore is a good model for Cys-loop receptor pores if the role of F16' is taken into consideration.

A non-linear regression analysis method for quantitative resolution of the stimulus-evoked compound action potential from rodent optic nerve.

The stimulus-evoked compound action potential (CAP) recorded from rodent optic nerve is polyphasic in profile, with total area under the CAP an index of nerve function. A decrease in CAP area signifies a decrease in the number of axons contributing to the CAP. A disadvantage of considering the CAP a uniform entity is that any distinctions between the axon-subpopulations contributing to the individual peaks go undetected. We illustrate two instances that demonstrate the advantages of resolving the CAP into its constituent peaks. The individual peaks of the CAP were quantified using curve-fitting procedures to describe the CAP as the sum of multiple Gaussian functions. The first example illustrates that the individual peaks comprising the CAP exhibit differential sensitivities to glucopenia, suggesting that the axons within the nerve cannot be considered a homogeneous population with regard to their metabolic characteristics. The second example illustrates that the complex waveform of the CAP recorded from the optic nerve of the hypomyelinated rumpshaker mutant mouse, comprising both positive and negative overlapping peaks, can be resolved into five individual peaks. In conclusion we show that assessing each individual peak of the CAP is a powerful analytic tool for identifying heterogeneous profiles of axon-subpopulations in the rodent optic nerve.