Changing the firing threshold for normal optic nerve axons by the application of infra-red laser light.

Normal optic nerve axons exhibit a temperature dependence, previously explained by a membrane potential hyperpolarization on warming. We now report that near infra-red laser light, delivered via a fibre optic light guide, also affects axonal membrane potential and threshold, at least partly through a photo-thermal effect. Application of light to optic nerve, at the recording site, gave rise to a local membrane potential hyperpolarization over a period of about a minute, and increased the size of the depolarizing after potential. Application near the site of electrical stimulation reversibly raised current-threshold, and the change in threshold recorded over minutes of irradiation was significantly increased by the application of the Ih blocker, ZD7288 (50 µM), indicating Ih limits the hyperpolarizing effect of light. Light application also had fast effects on nerve behaviour, increasing threshold without appreciable delay (within seconds), probably by a mechanism independent of kinetically fast K+ channels and Na+ channel inactivation, and hypothesized to be caused by reversible changes in myelin function.

The effects of temperature on the biophysical properties of optic nerve F-fibres.

In multiple sclerosis, exacerbation of symptoms with rising body temperature is associated with impulse conduction failure. The mechanism is not fully understood. Remarkably, normal optic nerve axons also show temperature dependent effects, with a fall in excitability with warming. Here we show two properties of optic nerve axons, accommodation and inward rectification (Ih), respond to temperature changes in a manner consistent with a temperature dependent membrane potential. As we could find no evidence for the functional expression of KV7.2 in the axons, using the K+ channel blocker tetraethylammonium ions, we suggest this may explain the membrane potential lability. In order to understand how the axonal membrane potential may show temperature dependence, we have developed a hypothesis involving the electroneutral movement of Na+ ions across the axon membrane, that increases with increasing temperature with an appropriate Q10. Part, but probably not all, of the electroneutral Na+ movement is eliminated by removing extracellular Cl- or exposure to bumetanide, consistent with the involvement of the transporter NKCC1. Numerical simulation suggests a change in membrane potential of - 15-20 mV mimics altering temperature between room and physiological in the largest axons.