Ion transport mechanisms and cell volume regulation: a study in a model transport epithelium

Aim: A wide variety of cell types are challenged by volume perturbations resulting from changes in extra- or intracellular osmolarity under a variety of physiological or pathophysiological conditions. Following hypertonic shrinkage or hypotonic swelling cells can re-adjust their volume by mechanisms known as regulatory volume decrease (RVD) or regulatory volume increase (RVI) respectively, which involve changes in the intracellular osmolyte concentration. In the present study we aimed to study the ion transport mechanisms responsible for cell volume homeostasis in a model salt-transporting epithelium, the intestine of the euryhaline teleost European eel. Methods: The study was carried out in the native tissue by using electrophysiological techniques, confocal microscopy, and morphometrical analysis of the epithelium exposed to isotonic and anisotonic conditions Results: The eel intestinal epithelium is able to perform a RVD and a RVI response following an hypotonic swelling or an hypertonic shrinkage respectively. The RVI response is accounted by the increased activity of the luminal Na+-K+-2Cl- cotransporter, while the RVD response is ensured by the activation of different K+ and anion conductive pathways on the apical and basolateral membranes of the epithelium. These responses are strongly dependent on cytoskeletal integrity, and require the involvement of several protein kinases, including PKC, myosin light chain kinases (MLCK), and al least three mitogen activated protein kinase (MAPK) subfamilies, extracellular signal regulated kinase (ERK)1/2, p38 MAPK, and c-Jun N-terminal kinase (JNK). Conclusions Cell volume of eel enterocytes appears under a tight and dynamic control involving the activity of several ion transport mechanisms and complex signalling pathways.