Alkaline and acid transients in cerebellar microenvironment

Area of Science:

• Neuroscience
• Physiology
• Biochemistry

Background:

• Extracellular pH (pHo) regulation is crucial for neuronal function.
• Understanding pH dynamics during physiological and pathological conditions is essential.

Purpose of the Study:

• To measure extracellular pH in the rat cerebellar cortex under various conditions.
• To investigate the role of neuronal activity, potassium concentration, spreading depression, and ischemia on pHo.
• To explore the involvement of carbonic anhydrase in pH homeostasis.

Main Methods:

• Utilized a liquid membrane ion-selective micropipette (ISM) for precise pHo measurements.
• Simultaneously measured extracellular potassium concentration ([K+]o) in many experiments.
• Applied local surface stimuli, superfusion with varying potassium levels, and induced ischemia and spreading depression.

Main Results:

• Neuronal stimulation caused initial alkaline shifts followed by prolonged acid shifts, influenced by stimulus parameters.
• [K+]o elevation led to progressive acidification, suggesting metabolic anion production (e.g., lactate).
• Spreading depression and ischemia induced distinct pHo and [K+]o changes, with carbonic anhydrase inhibition altering pHo homeostasis.

Conclusions:

• Neuronal activity and altered [K+]o significantly impact cerebellar extracellular pH.
• Metabolic processes and carbonic anhydrase are critical for maintaining brain extracellular microenvironment pH.
• Changes in strong ion difference, weak acid concentration, and PCO2 contribute to pH dynamics.