Potassium Cotransport with Sodium and Chloride in the Choroid Plexus

Abstract

The effects of loop diuretics and ion substitution on the 2-min uptake of K (86Rb as marker) were analyzed to obtain evidence for K cotransport with Na and Cl in the choroid plexus epithelium. The isolated plexuses, which were excised from lateral ventricles of adult rats, were bathed in artificial cerebrospinal fluid (aCSF). At concentrations of 10(-6) to 10(-4) M, the specific cotransport inhibitors, bumetanide and piretanide, suppressed uptake of K in a dose-dependent manner. Ouabain-insensitive K uptake was stimulated by preincubating the choroid plexus in aCSF very low in [Na] and [K], then incubating it in much higher concentrations of these cations; bumetanide (10(-4)M) blocked this stimulated uptake by 52%. Moreover, tissue preincubation in Na- or Cl-free medium, followed by incubation with normal concentrations of both ions, stimulated the ouabain-insensitive uptake of K from 15 (baseline) to 35 nmol/mg dry weight. This stimulation of K transport depended on the simultaneous presence of both Na and Cl in aCSF, and replacing either ion alone did not stimulate the ouabain-insensitive K uptake. Collectively, these findings, together with those from a previous pharmacological study of 22Na and 36Cl transport, constitute strong evidence for the cotransport of Na, K, and Cl in rat choroid plexus.

Bumetanide decreases canine cerebrospinal fluid production. In vivo evidence for NaCl cotransport in the central nervous system.

“…Studies of Betz (32) suggest that the cotransporter may also exist in cerebral capillaries. It is noted that Saito and Wright (31 ) In summary, data obtained in the present study along with the radioactive ion flux studies in dogs (27) and both in vivo (30) and in vitro CP studies (28,29) in rats strongly indicate the presence ofNaCl cotransport in mammalian CNS. Furthermore, the data from this study showing that bumetanide decreases CSF production, along with our previous data (33)(34)(35) showing that CSF ionic composition and CSF [Na'-Cl-] are not affected by bumetanide, indicate that NaCl cotransport is involved primarily in volume regulation of CSF.…”

“…However, in vitro studies of Johanson et al (28,29) using rats, and of Saito and Wright (31 ) using bullfrogs localize the cotransporter in CP cells. Studies of Betz (32) suggest that the cotransporter may also exist in cerebral capillaries.…”

“…Most recently, in a number of important in vitro studies (28)(29)(30) using rat isolated CP, Johanson and colleagues showed that choroidal cellular uptake of radioactive K+ (86Rb as the marker), Na' and Cl-was diminished up to -45-50% by pretreatment with bumetanide ( l0-5 to 10-4 mol/liter), indicating the presence ofa bumetanide-inhibitable Na, K, 2C1 cotransporter. Johanson and colleagues (30) also showed up to 30% reduction of radioactive Cl-flux from blood to CSF in rats pretreated with ethacrynic acid (50 mg/kg intravenously), another loop diuretic.…”

Distribution of sodium transporters and aquaporin-1 in the human choroid plexus

“…The NKCC inhibitor, bumetanide, inhibited Na ϩ secretion, thus indicating that NKCC1 supplies the CSF with Na ϩ and at the same time supplies the CSF with K ϩ to sustain the apical Na (2,14). In contrast, the same inhibitor was applied to show the involvement of NKCC2 in regulatory volume increase after exposure to hypertonic media, suggesting an inward transport under such conditions (44).…”

“…Studies of the mammalian choroid plexus suggest that the pivotal event in CSF secretion is the active ouabain-sensitive transport of Na ϩ from the epithelial cell to the CSF mediated by the apically positioned Na ϩ -K ϩ -ATPase (5,20). The apical Na ϩ -K ϩ -2Cl Ϫ cotransporter, NKCC1 (30), seems to contribute to Na ϩ secretion, because bumetanide inhibits CSF formation when applied apically (2,10,14). At the same time, NKCC1 would enrich the CSF with K ϩ to feed the apical Na ϩ -K ϩ -ATPase.…”