Intracellular pH of astrocytes increases rapidly with cortical stimulation

Modulation of intracellular pH is widely implicated in the control of cell growth and metabolism, yet little is known about intracellular pH and brain function. To determine how stimulation of brain may affect the intracellular pH of mammalian glial cells, rat cortical astrocytes were studied for the first time in vivo using pH-sensitive electrodes of submicron caliber. Stimulation of the cortical surface caused a cytoplasmic alkaline shift of tenths of a pH within seconds. Cessation of induced electrical activity was followed by pH recovery and a small acid rebound. Recordings obtained during cortical-spreading depression revealed similar but generally larger intracellular pH shifts. Production of metabolic acids is known to occur when the brain is stimulated and has led to the long-held presumption that brain cells accordingly become more acidic. The observation that glia initially become more alkaline during electrical activity is thus paradoxical. The correlation of glial alkalinization with evoked electrical activity suggests that modulation of intracellular pH of glia may have important functional implications.