Astrocytes of the central nervous system (CNS) and, more recently, myelinating Schwann cells of the peripheral nervous system (PNS) have been assigned a metabolic role as the result of their unique possession of glycogen and supply of lactate as an energy source to neurones (Brown et al., 2003, 2012). Glutamate was one of the first suggested metabolic signals between neurones and glia when the astrocyte-neuron lactate shuttle hypothesis (ANLSH) was proposed (Pellerin & Magistretti, 1994). However, glutamate is not a universal signal within the nervous system, unlike K+ which is released from axons of the CNS and PNS. Released during the repolarisation phase of the action potential, the amount of K+ efflux is a direct indication of neuronal firing frequency and therefore energy demand (Baylor & Nicholls, 1969). Moreover, it is widely considered that glial cell membrane potential, particularly astrocytes, is mediated solely by K+ (Kuffler et al., 1966). Within the CNS increased extracellular K+, as the result of increased neuronal activity, has been found to be tightly coupled to increased astrocytic glycolysis (Ruminot et al., 2019). A suggested mechanism involves K+ induced depolarisation of the astrocyte membrane potential triggering bicarbonate uptake via the sodium bicarbonate cotransporter. Bicarbonate-sensitive soluble adenylyl cyclase becomes activated resulting in an increase in cAMP which stimulates glycogen metabolism and thus lactate efflux (Choi et al., 2012). The aim of this study was to expand upon the role of K+ as a metabolic signal between axons and glia in both the CNS and PNS. All procedures were carried out in accordance with the Animals (Scientific Procedures) Act 1986 under appropriate authority of establishment, project and personal licenses. Adult male CD-1 mice were killed by cervical dislocation and decapitated. Optic and sciatic nerves, to represent the CNS and PNS respectively, were dissected and placed in a superfusion chamber, superfused with aerated control aCSF (10mM glucose and 3mM K+) at 37°C. Lactate biosensors (Sarissa Biomedical) were used to record real-time lactate release from the nerve into the bath solution. Suction electrodes were used to stimulate the nerve during high frequency stimulus (HFS) protocols. Superfusion of aCSF containing K+ above and below 3mM increased and decreased, respectively, the steady state concentration of lactate recorded; a relationship that was found to be logarithmic for both nerves (slope= 75.6 and 5.6 µM lactate/mM K+, optic (n=3) and sciatic (n=5) respectively). HFS of the optic nerve was then used to induce increased extracellular K+ directly from axons as the result of increased axonal firing (Connors et al., 1982). Increasing the frequency of stimulation increased the concentration of lactate detected by the biosensor up to ~50Hz, after which further increase in stimulation frequency caused no further rise in lactate release (n=3). The consistency of this preliminary data between the optic and sciatic nerve in response to changes in extracellular K+ suggests a promising universal role of K+ as an axon-glia metabolic signal within both the CNS and PNS. Furthermore, the logarithmic relationship observed implies changes in glial cell membrane potential influence lactate efflux.