Cell Volume Regulation in Cardiac Myocytes: A Leaky Boat Gets a New Bilge Pump

The fundamental precepts by which animal cells regulate their volume under isosmotic conditions have long been studied and are known, at least to a degree suitable for textbook exposition (for early references see Macknight and Leaf, 1977; Baumgarten and Feher, 2001). The usual starting point for accounts of this subject is the so-called Donnan equilibrium in which the cell membrane is permeant to water and small ions but impermeant to one or more ionic species, often of colloidal size (Boyle and Conway, 1941; Overbeek, 1956). With polyvalent intracellular macromolecules as the only impermeant species, a Donnan system does not establish a true equilibrium. To satisfy macroscopic electroneutrality, there is an equal accumulation of counter-ions and exclusion of co-ions on side of the membrane with the impermeant polyvalent macromolecules, and consequently, an osmotic pressure difference develops across the membrane that is...