Isovolumetric regulation mechanisms in cultured cerebellar granule neurons

Tuz, Karina; Ordaz, Benito; Vaca, Luis; Quesada, O.; Pasantes‐Morales, Herminia

doi:10.1046/j.1471-4159.2001.00546.x

Cited by 35 publications

(18 citation statements)

References 27 publications

(44 reference statements)

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“…1). Neurochemical studies suggested that taurine has a neuroprotective function, which is achieved by its action as an antioxidant and osmolyte, [1][2][3] and this is also supported by the retinal dysfunction resulting from a lack of taurine in humans and by severe retinal degeneration in TauT gene knockout mice. 7,20) Interestingly, during the abundance of taurine in the retina, low activity of the rate-limiting enzyme in taurine biosynthesis was reported in the retina, 21) showing a possible story that the regulation of the retinal taurine concentration is carried out through the transport system for taurine at the BRB.…”

Section: Taurine Transport Across the Brbmentioning

confidence: 97%

“…[1][2][3] Molecular identification and transport study have shown the cellular transport of taurine mediated by Na + -and Cl − -dependent transporters, such as taurine transporter (TauT/ SLC6A6) and mouse γ-aminobutyric acid (GABA) transporter 3 (GAT3/SLC6A13, the orthologue of rat GAT2), that have high (K m =43 µM) 4) and moderate affinity (K m =540 µM), 5) respectively (Table 1). A recent report has also shown that proton-coupled amino acid transporter 1 (PAT1/SLC36A1) is assumed to transport taurine with a low affinity (K m =7.5 mM).…”

Section: Introductionmentioning

confidence: 99%

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Impact of SLC6A Transporters in Physiological Taurine Transport at the Blood–Retinal Barrier and in the Liver

Kubo

Akanuma

Hosoya

2016

Biological & Pharmaceutical Bulletin

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Cumulative studies showed that taurine (2-aminoethanesulfonic acid) contributes to a variety of physiological events. Transport study suggested the cellular taurine transport in an Na -and Cl -dependent manner, and the several members of SLC6A family have been shown as taurine transporter. At the inner blood-retinal barrier (BRB), taurine transporter (TauT/SLC6A) is involved in the transport of taurine to the retina from the circulating blood. The involvement of TauT is also suggested in γ-aminobutyric acid (GABA) transport at the inner BRB, and its role is assumed in the elimination of GABA from the retinal interstitial fluid. In the retina, taurine is thought to be a major organic osmolyte, and its influx and efflux through TauT and volume-sensitive organic osmolyte and anion channel (VSOAC) in Müller cells regulate the osmolarity in the retinal microenvironment to maintain a healthy retina. In the liver, hepatocytes take up taurine via GABA transporter 2 (GAT2/SLC6A13, the orthologue of mouse GAT3) expressed at the sinusoidal membrane of periportal hepatocytes, contributing to the metabolism of bile acid. Site-directed mutagenesis study suggests amino acid residues that are crucial in the recognition of substrates by GATs and TauT. The evidence suggests the physiological impact of taurine transporters in tissues.

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Section: Taurine Transport Across the Brbmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Impact of SLC6A Transporters in Physiological Taurine Transport at the Blood–Retinal Barrier and in the Liver

Kubo

Akanuma

Hosoya

2016

Biological & Pharmaceutical Bulletin

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“…Another member of the TRP channel family, TRPV2, seems to participate in RVI via an interesting connection with the electroneutral cotransporter NKCC, which as previously mentioned is a main effector in RVI. The suggested mechanistic chain of events relating TRPV2 channels and RVI involves a TRPV2-dependent Tuz et al, 2001;Ordaz et al, 2004. accelerated depolarization followed by Ca 21 release from intracellular sources and the subsequent phosphorylation of STE20/SPS1-related proline/alanine-rich kinases (SPAKs), which is essential for activation of NKCC. This proposed pathway is supported by studies in skeletal muscle showing that expression of TRPV2 negative dominant reduces the RVI efficiency at the time that depolarization is impaired and the Ca 21 response is diminished (Zanou et al, 2015).…”

Section: Channel-transporter Interactions In Regulatory Volume Increasementioning

confidence: 99%

“…Taurine is particularly suitable for an osmolyte role since it is largely free in the cytosol, is not a protein amino acid, and participates in few reactions in the cell (Pasantes-Morales et al, 1998). Compared with other osmolytes, taurine shows the largest efflux (9-to 22-fold) and the lowest osmolarity threshold (Tuz et al, 2001), which could reflect a higher efficiency of the taurine efflux pathway or more availability of taurine pools for release compared with osmolytes involved in other cell functions.…”

mentioning

confidence: 98%

Channels and Volume Changes in the Life and Death of the Cell

Pasantes‐Morales

2016

Mol Pharmacol

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Volume changes deviating from original cell volume represent a major challenge for cellular homeostasis. Cell volume may be altered either by variations in the external osmolarity or by disturbances in the transmembrane ion gradients that generate an osmotic imbalance. Cells respond to anisotonicity-induced volume changes by active regulatory mechanisms that modify the intracellular/extracellular concentrations of K 1 , Cl -, Na 1 , and organic osmolytes in the direction necessary to reestablish the osmotic equilibrium. Corrective osmolyte fluxes permeate across channels that have a relevant role in cell volume regulation. Channels also participate as causal actors in necrotic swelling and apoptotic volume decrease. This is an overview of the types of channels involved in either corrective or pathologic changes in cell volume. The review also underlines the contribution of transient receptor potential (TRP) channels, notably TRPV4, in volume regulation after swelling and describes the role of other TRPs in volume changes linked to apoptosis and necrosis. Lastly we discuss findings showing that multimers derived from LRRC8A (leucine-rich repeat containing 8A) gene are structural components of the volume-regulated Cl -channel (VRAC), and we underline the intriguing possibility that different heteromer combinations comprise channels with different intrinsic properties that allow permeation of the heterogenous group of molecules acting as organic osmolytes.

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“…Organic osmolytes also participate in the volume regulatory process. Among the amino acids playing a role as osmolytes, taurine is a major osmoregulator, being preferentially lost during cell swelling [5]. Other amino acids, glutamate, aspartate, GABA and alanine, are also released from brain cells upon swelling [3,4,6].…”

Section: Introductionmentioning

confidence: 99%

Regulatory Volume Decrease in Neural Precursor Cells: Taurine Efflux and Gene Microarray Analysis

Hernández-Benítez¹,

Sedeño-Cortés²,

Ramos‐Mandujano³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Neural stem/ progenitor cells (NPCs) endure important changes in cell volume during growth, proliferation and migration. As a first approach to know about NPC response to cell volume changes, the Regulatory Volume Decrease (RVD) subsequent to hypotonic swelling was investigated. Methods: NPCs obtained from the mesencephalon and the subventricular zone of embryonic and adult mice, respectively, were grown and cultured as neurospheres. Cell volume changes were measured by large-angle light-scattering and taurine efflux by [³H]-taurine. Expression of genes encoding molecules related to RVD was analysed using a DNA microarray obtained from NPC samples. Results: Embryonic and adult NPCs exposed to osmolarity reduction (H15, H30, H40) exhibited rapid swelling followed by RVD. The magnitude, efficiency and pharmacological profile, of RVD and of [³H]-taurine osmosensitive efflux were comparable to those found in cultured brain cells, astrocytes and neurons. The relative expression of genes encoding molecules related to volume regulation, i.e. K⁺ and Cl^- channels, cotransporters, exchangers and aquaporins were identified in NPCs. Conclusion: NPCs show the ability to respond to hypotonic-evoked volume changes by adaptative recovery processes, similar to those found in other cultured brain cells. Genes related to molecules involved in RVD were found expressed in NPCs.

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Isovolumetric regulation mechanisms in cultured cerebellar granule neurons

Abstract: Cultured cerebellar granule neurons exposed to gradual reductions in osmolarity (2 1.8 mOsm/min) maintained constant volume up to 2 50% external osmolarity (p o

Cited by 35 publications

References 27 publications

Impact of SLC6A Transporters in Physiological Taurine Transport at the Blood–Retinal Barrier and in the Liver

Impact of SLC6A Transporters in Physiological Taurine Transport at the Blood–Retinal Barrier and in the Liver

Channels and Volume Changes in the Life and Death of the Cell

Regulatory Volume Decrease in Neural Precursor Cells: Taurine Efflux and Gene Microarray Analysis

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