Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB267

Poster Communications

Metabolically induced changes of nerve conduction velocity of spinal fibers in vivo in mice

P. Dibaj1, E. Schomburg1

1. Max-Planck-Institute for Experimental Medicine, Göttingen, Germany.

The conduction velocity of a nerve fiber is not constant but may be modified. We now investigated the influence of acute metabolic changes on nerve conduction velocity (NCV) of spinal fibers in mice in vivo. We developed an electrophysiological set-up for in vivo recording of CNS fibers in the fasciculus gracilis of the spinal dorsal column in anesthetized mice (initially injection of pentobarbital 80 mg/kg intraperitoneal, continuance intravenously with methohexital 40-60 mg/kg/h; artificially ventilated; ECG, core body temperature and blood O2 saturation permanently monitored for control of the anesthetic state; cf. P. Dibaj and E. D. Schomburg 20171) and measured NCV under different metabolic conditions: a) under low and high anesthetic state indicated by relatively high and low heart rate, respectively; b) under normoxia and hypoxia. Increasing the anesthetic state as well as decreasing the oxygen saturation in the blood led to a decrease of NCV indicating an immediate influence of acute metabolic changes on the speed of signal propagation in spinal nerve fibers. The decrease of NCV under the above mentioned different systemic metabolic challenges was rescued by local supply of lactate which was already shown to be secreted by glial cells and metabolized by axons for ATP generation. Metabolic support of axons by glial cells is impaired in ALS, which considerably contribute to the pathophysiological progress of axonal damage during the course of the disease. In the ALS mouse model SOD1G93A, we observed an improvement of the decreased NCV in clinically affected mice after lactate supply. Thus, local energy supply with lactate leads to a compensation of metabolically induced changes of the NCV of spinal fibers in vivo, not only under acute systemic impairment like high anesthesia or hypoxia but also in the chronic paradigm of ALS. It will be discussed if the supplied lactate increases the availability of ATP in axons. The increased ATP would then improve the activity of the ion channels of the metabolically impaired axons leading to an accelerated depolarization and thus to an increased NCV.

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