Review and Hypothesis: A Potential Common Link Between Glial Cells, Calcium Changes, Modulation of Synaptic Transmission, Spreading Depression, Migraine, and Epilepsy-H.

There is significant evidence to support the notion that glial cells can modulate the strength of synaptic connections between nerve cells, and it has further been suggested that alterations in intracellular calcium are likely to play a key role in this process. However, the molecular mechanism(s) by which glial cells modulate neuronal signaling remains contentiously debated. Recent experiments have suggested that alterations in extracellular H efflux initiated by extracellular ATP may play a key role in the modulation of synaptic strength by radial glial cells in the retina and astrocytes throughout the brain.

Extracellular ATP-Induced Alterations in Extracellular H Fluxes From Cultured Cortical and Hippocampal Astrocytes.

Small alterations in the level of extracellular H can profoundly alter neuronal activity throughout the nervous system. In this study, self-referencing H-selective microelectrodes were used to examine extracellular H fluxes from individual astrocytes. Activation of astrocytes cultured from mouse hippocampus and rat cortex with extracellular ATP produced a pronounced increase in extracellular H flux.