Physiological Roles of Aquaporins in the Choroid Plexus

Abstract

The choroid plexus is a specialized tissue that lines subdomains within the four ventricles of the brain where most of the cerebrospinal fluid is produced. Maintenance of an equilibrium in volume and composition of the cerebrospinal fluid (CSF) is vital for a normal brain function, ensuring an optimal environment for the neurons. The necessarily high water permeability of the choroid plexus barrier is made possible by the abundant expression of a water channel, Aquaporin-1 (AQP1), on the apical side of the membrane from early stages of development through adulthood. Data from studies of AQP1 suggest that it also can contribute as a gated ion channel, and suggest that the AQP1-mediated ionic conductance has physiological significance for the regulation of cerebrospinal fluid secretion. The regulation of AQP1 ion channels could be one of several transport mechanisms that contribute to the decreased CSF secretion in response to endogenous signaling molecules such as atrial natriuretic peptide. Numerous classes of ion channels and transporters are targeted specifically to each side of the cellular membrane, and they all work in concert to secrete CSF. Several signaling cascades have a direct effect on transporters and ion channels present in the choroid plexus epithelium, altering their transport activity and therefore modulating the net transcellular movement of solutes and water. Several neurotransmitters, neuropeptides, and growth factors can influence CSF secretion by direct effect on transport mechanisms of the epithelium. The mammalian choroid plexus receives innervation from noradrenergic sympathetic fibers, cholinergic and peptidergic fibers that modulate CSF secretion. Water imbalance in the brain can have life-threatening consequences resulting from altered excitability and neurodegeneration, disruption of the supply of nutrients, loss of signaling molecules, and the accumulation of unwanted toxins and metabolites. Understanding the mechanisms involved in the modulation of CSF secretion is of fundamental importance. An appreciation of AQP1 as an ion channel in addition to its role as a water channel should offer new targets for therapeutic strategies in diseases involving water imbalance in the brain.