Parallel Changes in Intracellular Water Volume and pH Induced by NH3/NH4+Exposure in Single Neuroblastoma Cells

Increased blood levels of ammonia (NH3) and ammonium (NH4(+)), i.e. hyperammonemia, leads to cellular brain edema in humans with acute liver failure. The pathophysiology of this edema is poorly understood. This is partly due to incomplete understanding of the osmotic effects of the pair NH3/NH4(+) at the cellular and molecular levels. Cell exposure to solutions containing NH3/NH4(+) elicits changes in intracellular pH (pHi), which can in turn affect cell water volume (CWV) by activating transport mechanisms that produce net gain or loss of solutes and water. The occurrence of CWV changes caused by NH3/NH4(+) has long been suspected, but the mechanisms, magnitude and kinetics of these changes remain unknown.