Extracellular pH and stimulated neurons

Area of Science:

• Neuroscience
• Physiology
• Biochemistry

Background:

• Extracellular pH (pHe) dynamics are crucial for neuronal function.
• Understanding ion fluxes and their impact on pHe is essential for comprehending neural activity.

Purpose of the Study:

• To investigate dynamic changes in extracellular pH (pHe) and ion concentrations (K+, Ca2+) during neural activity.
• To elucidate the mechanisms underlying pHe homeostasis and stimulation-induced pHe shifts in the spinal cord.

Main Methods:

• Utilized ion-sensitive microelectrodes to monitor real-time pHe and ion concentrations in isolated frog spinal cords and in vivo rat spinal cords.
• Applied repetitive electrical stimulation to afferent inputs and adequate stimuli to the skin.
• Employed specific inhibitors targeting ion transport mechanisms (Na+/H+ exchange, K+-Cl- co-transport, Cl-/HCO3- exchange, Na+/K+ pump, carbonic anhydrase) and a metabolic blocker (NaF).

Main Results:

• Electrical stimulation induced triphasic pHe changes (alkaline-acid-acid or alkaline-acid-alkaline), predominantly in lower dorsal horns.
• A transient acid shift of 0.15-0.25 pH units was observed during stimulation.
• Inhibition of key ion transporters and carbonic anhydrase impaired pHe homeostasis and reduced stimulation-induced pHe changes.
• NaF did not affect pHe changes, suggesting lactate accumulation is not the primary driver.

Conclusions:

• Stimulation-evoked pHe changes are not solely due to lactate accumulation.
• pHe homeostasis mechanisms involving ion transporters and carbonic anhydrase are critical for regulating pHe during neural activity.
• Observed pHe shifts can influence neuronal excitability, ion channel permeability, and glial cell function.