Uptake of locally applied deoxyglucose, glucose and lactate by axons and Schwann cells of rat vagus nerve

We asked whether, in a steady state, neurons and glial cells both take up glucose sufficient for their energy requirements, or whether glial cells take up a disproportionate amount and transfer metabolic substrate to neurons. A desheathed rat vagus nerve was held crossways in a laminar flow perfusion chamber and stimulated at 2 Hz. C-14-labelled substrate was applied from a micropipette for 5 min over a < 0.6 min band of the surface of the nerve. After 10-55 min incubation, the nerve was lyophilized and the longitudinal distribution of radioactivity measured. When the weakly metabolizable analogue of glucose, 2-deoxy-[U-C-14]D-glucose (*DG), was applied, the profiles of the radioactivity broadened with time, reaching distances several times the mean length of the Schwann cells (0.32 min; most of the Schwann cells are non-myelinating). The profiles were well fitted by curves calculated for diffusion in a single compartment, the mean diffusion coefficient being 463 +/- 34 mum(2) s(-1) (+/- s.e.m., n = 16). Applications of *DG were repeated in the presence of the gap junction blocker, carbenoxolone (100 muM). The profiles were now narrower and better fitted with two compartments. One compartment had a coefficient not significantly different from that in the absence of the gap junction blocker (axons), the other compartment had a coefficient of 204 +/- 24 mum(2) s(-1), n = 4. Addition of the gap junction blocker 18-alpha-glycyrrhetinic acid, or blocking electrical activity with TTX, also reduced longitudinal diffusion. Ascribing the compartment in which diffusion was reduced by these treatments to non-myelinating Schwann cells, we conclude that 78.0 +/- 3.6 % (n = 9) of the uptake of *DG was into Schwann cells. This suggests that there was transfer of metabolic substrate from Schwann cells to axons. Local application of [C-14] glucose or [C-14] lactate led to variable labelling along the length of the nerve, but with both substrates narrow peaks were often present at the application site; these were greatly reduced by subsequent treatment with amylase, a glycogen-degrading enzyme.