Modulation of CNS excitability by water movement. the D2O effects on the non-linear neuron-glial dynamics

Macroscopic spatiotemporal patterns arising in grey matter may explain the clinical manifestations of several functional neurological syndromes (migraine aura, epilepsies). Detailed descriptions of these patterns in central grey matter and their physicochemical or pharmacological manipulations can be useful in many scientific fields ranging from drug design to functional brain imaging. These evanescent dynamic structures are electrochemical in nature and show macroscopic tissue polarization due to coupled and macroscopic flow of ions and water across, along and between neuronal and glial membranes. So far the importance of the water flow in the CNS functional syndromes has been examined by manipulations of water channels aquaporines (AQP). In this paper we show the result of substituting H2O for D2O in retinal spreading depression experiments. This inverts the present logic by changing the flow in the water channels in intact tissue and observing the evolution of electrochemical patterns and recording the optical profiles of excitation waves in isolated chick retinas. D2O flow through AQPs is ~20% slower than that of H2O. The slower flux disturbs the tight coupling between ion and water flows across membranes and slowdown the Na-KATPase rate of change with metabolic consequences for the tissue. The whole tissue excitability shifts in a non-stationary manner toward a non-excitable state.