A macrophage cell model for pH and volume regulation.

Area of Science:

• Cellular physiology
• Computational biology
• Biophysics

Background:

• Macrophage (mphi) pH and volume regulation are critical cellular processes.
• Ammonia prepulse challenges are used to study cellular acid-base balance.
• Conventional methods for quantifying proton (H+) efflux have limitations.

Purpose of the Study:

• To develop a whole-cell model of a macrophage to simulate pH and volume regulation.
• To investigate the accuracy of experimental methods for measuring proton (H+) efflux.
• To analyze the complex interactions influencing acid extrusion during recovery from an acid load.

Main Methods:

• Development of a whole-cell model of a macrophage (mphi).
• Simulation of pH and volume regulation during an NH4Cl prepulse challenge.
• Analysis of transporter-mediated H+ efflux and its quantification.

Main Results:

• The mphi model successfully mimicked experimental data for intracellular pH (pH(i)) and cell volume (Vol(i)) changes.
• Significant problems were identified in quantifying H+ efflux solely from pH(i) recovery data.
• Model predictions revealed complex interactions between H+ extrusion, buffering, and ammonia efflux.

Conclusions:

• Conventional methods for estimating H+ extrusion current (I(H)) are problematic due to unconsidered factors.
• Estimations of I(H) must account for the perturbation of cytoplasmic buffering during prepulse challenges.
• The developed whole-cell model has potential for characterizing pH and volume regulation in other non-excitable cells like microglia and T-lymphocytes.