Mechanisms of CSF secretion by the choroid plexus

Abstract

The epithelial cells of the choroid plexus secrete cerebrospinal fluid (CSF), by a process that involves the movement of Na+, Cl− and HCO3− from the blood to the ventricles of the brain. This creates the osmotic gradient, which drives the secretion of H2O. The unidirectional movement of the ions is achieved due to the polarity of the epithelium, i.e., the ion transport proteins in the blood‐facing (basolateral) are different to those in the ventricular (apical) membranes. Saito and Wright (1983) proposed a model for secretion by the amphibian choroid plexus, in which secretion was dependent on activity of HCO3− channels in the apical membrane. The patch clamp method has now been used to study the ion channels expressed in rat choroid plexus. Two potassium channels have been observed that have a role in maintaining the membrane potential of the epithelial cell, and in regulating the transport of K+ across the epithelium. An inward‐rectifying anion channel has also been identified, which is closely related to ClC‐2 channels, and has a significant HCO3− permeability. This channel is expressed in the apical membrane of the epithelium where it may play an important role in CSF secretion. A model of CSF secretion by the mammalian choroid plexus is proposed that accommodates these channels and other data on the expression of transport proteins in the choroid plexus. Microsc. Res. Tech. 52:49–59, 2001. © 2001 Wiley‐Liss, Inc.

Ion Channel Function of Aquaporin-1 Natively Expressed in Choroid Plexus

“…Selective loss of the cGMP-stimulated cationic current after two methods of AQP1-small interfering RNA (siRNA) treatment confirms that the conductance cannot be attributed to other endogenous ion channels in the choroid plexus (Hung et al, 1993;Speake et al, 2001. Our data are the first to show ion channel function in a native aquaporin and suggest the promise that aquaporin ionic conductances have physiologically relevant functions in regulatory mechanisms of transmembrane fluid transport in brain and other tissues.…”

“…We show that natively expressed AQP1 functions as a cGMP-gated ion channel and that the ionic conductance modulates fluid transport in the choroid plexus in a manner consistent with the observed effects in vivo. The similarities between AQP1 channel properties in the choroid plexus and the oocyte expression system, and the effective knockdown by AQP1-siRNAs, confirm that this conductance cannot be attributed to other channels known to be expressed in the choroid plexus (Hung et al, 1993;Speake et al, 2001.…”

“…Endogenous K ϩ and Cl Ϫ currents known to be present in the choroid plexus (Garner and Brown, 1992;Kotera and Brown, 1994;Speake et al, 2001Speake et al, , 2002 were minimized by ionic substitution of NaCl and KCl with Cs-methanesulfonate, resulting in a low initial conductance before application of cGMP agonists (Fig. 2a).…”

“…AQP1 is abundant in the choroid plexus, a tissue bordering brain ventricles that produces CSF by active Na ϩ transport and concomitant water flux from blood to brain (Wright and Saito, 1986;Speake et al, 2001). Atrial natriuretic peptide (ANP) receptors in choroid plexus epithelia couple to guanylate cyclase, stimulating cGMP generation (Tsutsumi et al, 1987;Israel et al, 1988) and inhibiting CSF production (Steardo and Nathanson, 1987).…”

KCNE2 and the K+channel

“…48,49 Accordingly, the flux of ions from the basolateral (blood) side to the apical (CSF) side of the CPe must be exquisitely regulated, as it is highly influential upon physiological aspects of the CNS including neuronal function and intracranial pressure [50][51][52][53] (Fig. 2B).…”