Cell volume and pH regulation by the Amphiuma red blood cell: a model for hypoxia-induced cell injury

The Amphiuma red blood cell is one of the model systems employed early in the study of vertebrate cell volume regulation. Following both cell swelling and shrinkage the Amphiuma red blood cell demonstrates volume regulation to virtual completion in 90-120 min. When swollen the Amphiuma red blood cell loses K, Cl and osmotically obliged water, while following shrinkage volume regulation is the result of Na, Cl and therefore water uptake. The main contribution of the Amphiuma red cell as a model is that it was the first cell in which volume regulation was demonstrated to be electroneutral and more specifically that K/H and Na/H exchangers were responsible for regulation following cell swelling and shrinkage, respectively. Additionally, the Amphiuma red blood cell K/H and Na/H exchangers have been demonstrated to function in a pH regulatory capacity. The latter observation in turn led to the demonstration of the mutually exclusive and contradictory nature of volume and pH regulation predicted upon Na/H exchanger activity. These observations prompted our recent investigations of the Na/H exchanger as a contributor to hypoxia-induced cell damage, using the rabbit heart as a model. These studies illustrated that Na, and Ca imbalances characteristic of hypoxia-induced cell damage are ultimately referable to the Na/H exchanger's function in a pH regulatory capacity, which contributes fundamentally to cell volume and Ca derangement and ultimately cell injury.