Regulation of cell volume via microvillar ion channels

A novel mechanism of cellular volume regulation is presented, which ensues from the recently introduced concept of transport and ion channel regulatio n via microvillar structures (Lange K, 1999, J Cell Physiol 180:19-35). Acc ording to th is notion, the activity of ion channels and transporter protei ns located on microvilli of differentiated cells is regulated by changes in the structural organization of the bundle of actin filaments in the microv illar shaft region. Cells with microvillar surfaces represent two-compartme nt systems consisting of the cytoplasm on the one side and the sum of the m icrovillar lip (or, entrance) compartments on the other side. The two compa rtments are separated by the microvillar actin filament bundle acting as di ffusion barrier ions and other solutes. The specific organization of ion an d water channels on the surface of microvillar cell types enables this two- compartment system to respond to hypo- and hyperosmotic conditions by activ ation of ionic fluxes along electrochemical gradients. Hypotonic exposure r esults in swelling of the cytoplasmic compartment accompanied by a correspo nding reduction in the length of the microvillar diffusion barrier, allowin g osmolyte efflux and regulatory volume decrease (RVD). Hypertonic conditio ns, which cause shortening of the diffusion barrier via swelling of the ent rance compartment, allow osmolyte influx for regulatory volume increase (RV I). Swelling of either the cytoplasmic or the entrance compartment, by usin g membrane portions of the microvillar shafts for surface enlargement, acti vates ion fluxes between the cytoplasm and the entrance compartment by shor tening of microvilli. The pool of available membrane lipids used for cell s welling, which is proportional to length and number of microvilli per cell, represents the sensor system that directly translates surface enlargements into activation of ion channels. Thus, the use of additional membrane comp onents for osmotic swelling or other types of surface-expanding shape chang es (such as the volume-invariant cell spreading or stretching) directly reg ulates influx and efflux activities of microvillar ion channels. The propos ed mechanism of ion flux regulation also applies to the physiological main functions of epithelial cells and the auxiliary action of swelling-induced ATP release. Furthermore, the microvillar entrance compartment, as a finely dispersed ion-accessible peripheral space, represents a cellular sensor fo r environmental ionic/osmotic conditions able to detect concentration gradi ents with high lateral resolution. Volume regulation via microvillar surfac es is only one special aspect of the general property of mechanosensitivity of microvillar ionic pathways. (C) 2000 Wiley-Liss, Inc.