Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse.

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS).

The critical role of logarithmic transformation in Nernstian equilibrium potential calculations.

The membrane potential, arising from uneven distribution of ions across cell membranes containing selectively permeable ion channels, is of fundamental importance to cell signaling. The necessity of maintaining the membrane potential may be appreciated by expressing Ohm's law as current = voltage/resistance and recognizing that no current flows when voltage = 0, i.e., transmembrane voltage gradients, created by uneven transmembrane ion concentrations, are an absolute requirement for the generation of currents that precipitate the action and synaptic potentials that consume >80% of the brain's energy budget and underlie the electrical activity that defines brain function. The concept of the equilibrium potential is vital to understanding the origins of the membrane potential. The equilibrium potential defines a potential at which there is no net transmembrane ion flux, where the work created by the concentration gradient is balanced by the transmembrane voltage difference, and derives from a relationship describing the work done by the diffusion of ions down a concentration gradient. The Nernst equation predicts the equilibrium potential and, as such, is fundamental to understanding the interplay between transmembrane ion concentrations and equilibrium potentials. Logarithmic transformation of the ratio of internal and external ion concentrations lies at the heart of the Nernst equation, but most undergraduate neuroscience students have little understanding of the logarithmic function. To compound this, no current undergraduate neuroscience textbooks describe the effect of logarithmic transformation in appreciable detail, leaving the majority of students with little insight into how ion concentrations determine, or how ion perturbations alter, the membrane potential.