Acid- and Volume-Sensitive Chloride Currents in Microglial Cells

Area of Science:

• Cell Biology
• Ion Channel Physiology
• Neuroscience

Background:

• Microglia play critical roles in central nervous system inflammation and injury.
• Acidosis is a common feature in pathophysiological conditions such as stroke and ischemia.
• The function of acid-sensitive outwardly rectifying (ASOR) anion currents in microglia remains largely unknown.

Purpose of the Study:

• To characterize the ASOR current in BV-2 microglial cells.
• To investigate the interplay between ASOR and volume-sensitive outwardly rectifying (VSOR) chloride currents.
• To determine the impact of acidosis on microglial cell volume regulation.

Main Methods:

• Patch clamp electrophysiology to measure ion currents and membrane potentials.
• Coulter method to assess mean cell volume.
• pH-sensitive dye BCECF to monitor intracellular pH.

Main Results:

• ASOR currents activated at acidic pH (≤ 5.0) with a specific anion permeability (I⁻ > Cl⁻ > gluconate⁻).
• ASOR currents were distinct from VSOR currents in their sensitivity to inhibitors (e.g., DCPIB, tamoxifen).
• Acidosis led to ASOR current activation, VSOR current inactivation, cell swelling, and impaired regulatory volume decrease.

Conclusions:

• Acidosis significantly disrupts microglial cell volume homeostasis by modulating ASOR and VSOR currents.
• The characterized ASOR current is a key player in microglial response to acidic environments.
• Impaired cell volume regulation due to ASOR activation may affect microglial functions like migration and phagocytosis during pathological events.