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Published on: July 17, 2011
Temporal fluctuations of voltage-gated proton currents in rat spinal microglia via pH-dependent and -independent
H Morihata1, J Kawawaki, H Sakai
1Department of Physiology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan.
Abstract:
Voltage-gated proton (H(+)) channels are unique mechanisms to extrude a massive amount of H(+), and are proposed to regulate intracellular pH of microglia during respiratory bursts. Temporal variations of the H(+) current were studied in rat spinal microglia cultivated on the glial cell layer using the voltage-ramp protocol. Repetitive applications of the large and long-lasting depolarization decreased the amplitudes of the H(+) current transiently and reversibly. This decrease was accompanied by a shift of the reversal potential to a more positive direction, indicating that a drop in the transmembrane pH gradient (delta pH) by the H(+) efflux through the channel reduced the current. The decline of the H(+) current during depolarizations was also observed in a rat microglial cell line (GMI-R1). An increase in the extracellular buffer suppressed the reduction of the current, suggesting that H(+) secreted into the extracellular space contributed to the drop in delta pH. On the other hand, the amplitudes of the H(+) current often fluctuated greatly at intervals of 5-20 min without changes in delta pH. These results suggest that the H(+) current of microglia is tuned via both delta pH-dependent and -independent mechanisms, which may regulate both microglial behavior and the pH environments of the surrounding neural tissue.
Insights
Voltage-gated proton channels in microglia help regulate intracellular pH. Their current is transiently reduced by depolarization due to pH changes, but also fluctuates independently, influencing microglial function.
Area of Science:
- Neuroscience
- Cell Biology
- Physiology
Background:
- Voltage-gated proton channels (H+) are crucial for H+ extrusion.
- These channels are proposed to regulate microglial intracellular pH during respiratory bursts.
Purpose of the Study:
- To investigate the temporal variations of H+ current in rat spinal microglia.
- To understand the mechanisms regulating H+ current in microglia.
Main Methods:
- Utilized the voltage-ramp protocol on cultured rat spinal microglia and a microglial cell line (GMI-R1).
- Studied the effects of repetitive depolarization and extracellular buffering on H+ current.
- Analyzed changes in reversal potential and transmembrane pH gradient (delta pH).
Main Results:
- Repetitive depolarization transiently decreased H+ current amplitude, linked to a drop in delta pH.
- Extracellular buffering attenuated current reduction, indicating H+ secretion impacts delta pH.
- H+ current also exhibited fluctuations independent of delta pH.
Conclusions:
- Microglial H+ current regulation involves both delta pH-dependent and -independent mechanisms.
- These regulatory mechanisms may influence microglial behavior and the pH of surrounding neural tissue.
