Extracellular ionic and volume changes: the role in glia-neuron interaction

Area of Science:

• Neuroscience
• Developmental Biology
• Physiology

Background:

• Extracellular ion concentrations, including potassium ([K+]e) and pH (pHe), dynamically change with neural activity.
• These changes are crucial for neuronal function and can be influenced by developmental stage and glial cell activity.

Purpose of the Study:

• To investigate activity-related changes in [K+]e and pHe in the rat spinal cord during postnatal development.
• To elucidate the cellular mechanisms underlying pH shifts, particularly the roles of glial cells and postsynaptic activity.

Main Methods:

• Utilized ion-selective microelectrodes to measure [K+]e and pHe in vivo and in isolated neonatal rat spinal cords.
• Studied extracellular space (ECS) parameters (volume fraction, tortuosity, uptake) affecting diffusion.
• Employed X-irradiation to inhibit gliogenesis and pharmacological agents (Mg2+, picrotoxin, acetazolamide, Ba2+, amiloride, SITS, glutamate, GABA) to probe mechanisms.

Main Results:

• Adult rats showed [K+]e increases of 2.0-3.5 mM and triphasic pHe changes with a dominant acid shift.
• Neonatal rats (P3-P6) exhibited higher [K+]e increases (up to 6.5 mM) and a dominant alkaline shift, which decreased with age.
• X-irradiation blocked the development of acid shifts and gliosis, while alkaline shifts were influenced by neurotransmitters and ion channel blockers.

Conclusions:

• Activity-related acid shifts in pHe are associated with mature glial cell membrane transport processes.
• Alkaline shifts in pHe originate from postsynaptic activity mediated by ligand-gated ion channels.
• Developmental changes in [K+]e and pHe reflect the maturation of glial and neuronal functions in the spinal cord.