Water transport and homeostasis as a major function of erythrocytes

Erythrocytes have long been known to change volumes and shapes in response to different salt concentrations. Aquaporin-1 (AQP1) was discovered in their membranes more than 20 years ago. The physiological roles of volume changes and AQP1 expression, however, have remained unclear. We propose that rapid water exchange through AQP1 coupled with large capacity for volume change may allow erythrocytes to play an important role in water regulation. In this study, we showed that erythrocytes in situ gradually reduced their volumes by 39% in response to the hyperosmotic corticomedullary gradient within mouse kidneys. AQP1 KO erythrocytes, however, displayed only minimal reduction. Constructing a microfluidic device resembling capillary flow with an extracellular fluorescent reporter demonstrated that water exchanges between erythrocytes and their hypotonic or hypertonic surroundings in vitro reached steady-state in about 60 ms. AQP1 KO erythrocytes, however, did not show significant change. To simulate the water ...