Whole cell Cl- conductances in mouse choroid plexus epithelial cells do not require CFTR expression

Kibble, Jonathan D.; Garner, C.; Colledge, William H.; Brown, S. M. P.; Kajita, Hidetoshi; Evans, Martin; Brown, Peter de Nully

doi:10.1152/ajpcell.1997.272.6.c1899

Cited by 36 publications

(35 citation statements)

References 11 publications

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“…Nonetheless, Cl − currents have been found in mouse choroid plexus epithelial cells that have many of the characteristics of ClC-2 but also display some differences, such as dependence on intracellular ATP [14]; in fact, it was found that those currents persisted in ClC-2 knockout mice, pointing to an unidentified channel with characteristics that overlap those of ClC-2 [30]. The lack of an antibody with convincing specificity for ClC-2 in fixed tissues [35] precluded localization of the protein to the apical or basolateral membrane in Reissner’s membrane, although the effective inhibition of the inward current by ClC-2 antibody supports a similar epitope on the underlying channel or an associated protein.…”

Section: Discussionmentioning

confidence: 99%

Inward-rectifier chloride currents in Reissner’s membrane epithelial cells

Kim

Marcus

2010

Biochemical and Biophysical Research Communications

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Sensory transduction in the cochlea depends on regulated ion secretion and absorption. Results of whole-organ experiments suggested that Reissner’s membrane may play a role in the control of luminal Cl−. We tested for the presence of Cl− transport pathways in isolated mouse Reissner’s membrane using whole-cell patch clamp recording and gene transcript analyses using RT-PCR. The current-voltage (I-V) relationship in the presence of symmetrical NMDG-Cl was strongly inward-rectifying at negative voltages, with a small outward current at positive voltages. The inward-rectifying component of the I-V curve had several properties similar to those of the ClC-2 Cl− channel. It was stimulated by extracellular acidity and inhibited by extracellular Cd2+, Zn2+, and intracellular ClC-2 antibody. Channel transcripts expressed include ClC-2, Slc26a7 and ClC-Ka, but not Cftr, ClC-1, ClCa1, ClCa2, ClCa3, ClCa4, Slc26a9, ClC-Kb, Best1, Best2, Best3 or the beta-subunit of ClC-K, barttin. ClC-2 is the only molecularly-identified channel present that is a strong inward rectifier. This study is the first report of conductive Cl− transport in epithelial cells of Reissner’s membrane and is consistent with an important role in endolymph anion homeostasis.

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Section: Discussionmentioning

confidence: 99%

Inward-rectifier chloride currents in Reissner’s membrane epithelial cells

Kim

Marcus

2010

Biochemical and Biophysical Research Communications

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“…Furthermore, ATP-binding cassette proteins such as CFTR and p-glycoprotein are known to regulate other Cl -channels [19]. This possibility remains to be investigated; however, the regulatory protein involved in the choroid plexus is unlikely to be CFTR, since the inward-rectifying Cl -conductance is not impaired in the choroid plexus of CF "knock-out" mice [13].…”

Section: Discussionmentioning

confidence: 99%

“…2.5 nS) observed in the presence of ATP[γ-S] and AMP-PNP are similar in size to the currents observed in the presence of phorbol esters or the residual currents not blocked by divalent cations. These currents may be carried by volume-sensitive Cl -channels which are also expressed in choroid plexus epithelial cells[12,13] …”

mentioning

confidence: 99%

Properties of the inward-rectifying Cl– channel in rat choroid plexus: regulation by intracellular messengers and inhibition by divalent cations

Kajita

Whitwell

Brown

2000

Pflugers Arch - Eur J Physiol

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The properties of the inward-rectifying Cl- conductance in rat choroid plexus epithelial cells were investigated to allow comparisons to be made with ClC-2. All experiments were performed using the whole-cell configuration of the patch-clamp method. The conductance was transiently activated using an electrode solution which contained 375 nM catalytic subunit of protein kinase A (PKA). PKA failed to activate the conductance, however, when cells were pre-incubated with phorbol esters, which activate protein kinase C [1 microM phorbol 12-myristate 13-acetate (PMA) and 1 microM phorbol 12,13-dibutyrate (PDBu)]. Sustained activation of the conductance by PKA was observed in Ca2+-free conditions (5 mM BAPTA in the electrode solution), or when 100 nM calphostin C, a PKC inhibitor, was added to the electrode solution. The inward-rectifying Cl- conductance in choroid plexus is therefore similar to ClC-2 in that it is inhibited by PKC. The inward-rectifying conductance was blocked when Cd2+ (30 and 300 microM) and Zn2+ (1, 30 and 300 microM) were added to the bath solution. ClC-2 channels are also blocked by Zn2+ and Cd2+. The magnitude of the inward conductance was dependent on the concentration of ATP in the electrode solution. The conductance was not observed when ATP in the electrode was replaced with non-hydrolysable ATP analogues [adenosine 5'-O-(3-thiotriphosphate) (ATP[gamma-S]) and 5'-adenylylimidodiphosphate (AMP-PNP)), but it was supported by UTP and GTP. These data contrast with those of previous studies in which ClC-2 channels were activated in the absence of ATP. In conclusion, the inward-rectifying Cl- channel in rat choroid plexus shares some properties with ClC-2 (inhibition by PKC and block by divalent cations), but differs in that it depends on intracellular ATP.

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“…Chloride transport into the CSF is regulated in part by an apically localized inward-rectifying chloride channel, which is activated by intracellular cyclic AMP (cAMP) signaling (Brown et al, 2004;Kibble et al, 1997). To investigate a possible mechanism leading to the elevated chloride level in mutant CSF, we measured the intracellular concentrations of cAMP in CP cells freshly isolated from 5-day-old mutant and wild-type mice.…”

Section: Tg737mentioning

confidence: 99%

Dysfunctional cilia lead to altered ependyma and choroid plexus function,and result in the formation of hydrocephalus

et al. 2005

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Cilia are complex organelles involved in sensory perception and fluid or cell movement. They are constructed through a highly conserved process called intraflagellar transport (IFT). Mutations in IFT genes, such as Tg737, result in severe developmental defects and disease. In the case of the Tg737orpk mutants, these pathological alterations include cystic kidney disease, biliary and pancreatic duct abnormalities, skeletal patterning defects, and hydrocephalus. Here, we explore the connection between cilia dysfunction and the development of hydrocephalus by using the Tg737orpk mutants. Our analysis indicates that cilia on cells of the brain ventricles of Tg737orpk mutant mice are severely malformed. On the ependymal cells, these defects lead to disorganized beating and impaired cerebrospinal fluid (CSF) movement. However, the loss of the cilia beat and CSF flow is not the initiating factor, as the pathology is present prior to the development of motile cilia on these cells and CSF flow is not impaired at early stages of the disease. Rather, our results suggest that loss of cilia leads to altered function of the choroid plexus epithelum, as evidenced by elevated intracellular cAMP levels and increased chloride concentration in the CSF. These data suggest that cilia function is necessary for regulating ion transport and CSF production, as well as for CSF flow through the ventricles.

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Whole cell Cl- conductances in mouse choroid plexus epithelial cells do not require CFTR expression

Cited by 36 publications

References 11 publications

Inward-rectifier chloride currents in Reissner’s membrane epithelial cells

Inward-rectifier chloride currents in Reissner’s membrane epithelial cells

Properties of the inward-rectifying Cl– channel in rat choroid plexus: regulation by intracellular messengers and inhibition by divalent cations

Dysfunctional cilia lead to altered ependyma and choroid plexus function,and result in the formation of hydrocephalus

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