Cardiac cell volume: crystal clear or murky waters? A comparison with other cell types

The osmolarity of bodily fluids is strictly controlled so that most cells do not experience changes in osmotic pressure under normal conditions, but osmotic changes can occur in pathological states such as ischemia, septic shock, and diabetic coma. The primary effect of a change in osmolarity is to acutely alter cell volume. If the osmolarity around a cell is decreased, the cell swells, and if increased, it shrinks. In order to tolerate changes in osmolarity, cells have evolved volume regulatory mechanisms activated by osmotic challenge to normalise cell volume and maintain normal function. In the heart, osmotic stress is encountered during a period of myocardial ischemia when metabolites such as lactate accumulate intracellularly and to a certain degree extracellularly, and cause cell swelling. This swelling may be exacerbated further on reperfusion when the hyperosmotic extracellular milieu is replaced by normosmotic blood. In this review, we describe the theory and mechanisms of volume regulation, and draw on findings in extracardiac tissues, such as kidney, whose responses to osmotic change are well characterised. We then describe cell volume regulation in the heart, with particular emphasis on the effect of myocardial ischemia. Finally, we describe the consequences of osmotic cell swelling for the cell and for the heart, and discuss the implications for antiarrhythmic drug efficacy. Using computer modelling, we have summated the changes induced by cell swelling, and predict that swelling will shorten the action potential. This finding indicates that cell swelling is an important component of the response to ischemia, a component modulating the excitability of the heart.