Characterization of the hypo-osmolarity-induced Ca2+ response in cultured rat astrocytes

Fischer, Richard; Schliess, Freimut; Häussinger, Dieter

doi:10.1002/(sici)1098-1136(199705)20:1<51::aid-glia5>3.0.co;2-8

Cited by 56 publications

(33 citation statements)

References 31 publications

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“…Lowering osmolarity enhances the release of multiple transmitters from neurons (Schousboe and Pasantes-Morales, 1992) and glia (Darby et al, 2003;Takano et al, 2005), some of which inhibit I M by releasing Ca 2ϩ from IP 3 -sensitive stores in the endoplasmic reticulum (Delmas and Brown, 2005). However, hyposmotic release of internally stored Ca 2ϩ was observed also in dissociated CA1 pyramidal cells devoid of contacts with other neurons or glia (Borgdorff et al, 2000), as well as in many cell types other than neurons (Fischer et al, 1997;Missiaen et al, 1997). Thus, the nature of the physicochemical mechanisms coupling extracellular hyposmolarity to Ca 2ϩ release from internal stores remains to be identified.…”

Section: Role Of Internal Camentioning

confidence: 99%

K_V7/M Channels Mediate Osmotic Modulation of Intrinsic Neuronal Excitability

Caspi¹,

Benninger²,

Yaari³

2009

J. Neurosci.

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Modest decreases in extracellular osmolarity induce brain hyperexcitability that may culminate in epileptic seizures. At the cellular level, moderate hyposmolarity markedly potentiates the intrinsic neuronal excitability of principal cortical neurons without significantly affecting their volume. The most conspicuous cellular effect of hyposmolarity is converting regular firing neurons to burst-firing mode. This effect is underlain by hyposmotic facilitation of the spike afterdepolarization (ADP), but its ionic mechanism is unknown. Because blockers of K V 7 (KCNQ) channels underlying neuronal M-type K ϩ currents (K V 7/M channels) also cause spike ADP facilitation and bursting, we hypothesized that lowering osmolarity inhibits these channels. Using current-and voltage-clamp recordings in CA1 pyramidal cells in situ, we have confirmed this hypothesis. Furthermore, we show that hyposmotic inhibition of K V 7/M channels is mediated by an increase in intracellular Ca 2ϩ concentration via release from internal stores but not via influx of extracellular Ca 2ϩ . Finally, we show that interfering with internal Ca 2ϩ -mediated inhibition of K V 7/M channels entirely protects against hyposmotic ADP facilitation and bursting, indicating the exclusivity of this novel mechanism in producing intrinsic neuronal hyperexcitability in hyposmotic conditions.

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Section: Role Of Internal Camentioning

confidence: 99%

K_V7/M Channels Mediate Osmotic Modulation of Intrinsic Neuronal Excitability

Caspi¹,

Benninger²,

Yaari³

2009

J. Neurosci.

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“…Cytotoxic edema refers to cell swelling that results from intracellular fluid accumulation that occurs during stroke, trauma, or hypoxia (Papadopoulos et al, 2004), and this can be reproduced in vitro by exposing cells to extracellular hypo-osmolarity (Fischer et al, 1997;Caprini et al, 2003). Several genes, including p75NTR, are activated in response to this treatment (Husson et al, 1996;Meisse et al, 1998;Michalke et al, 2000;Warskulat et al, 2001;Peterson and Bogenmann, 2003), but the mechanisms that support this response and its physiological significance remain uncertain.…”

Section: Introductionmentioning

confidence: 99%

Hypo-Osmolar Stress Induces p75NTR Expression by Activating Sp1-Dependent Transcription

Ramos¹,

Ho²,

Forté³

et al. 2007

J. Neurosci.

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Injury-induced expression of the p75 neurotrophin receptor (p75NTR) in the CNS facilitates neuronal apoptosis and prevents neuronal regrowth, but the mechanisms regulating p75NTR expression are poorly characterized. In this study, we showed that hypo-osmolarity induces p75NTR expression in primary neurons, and, using a comparative genomics approach, we identified conserved elements in the 25 kb upstream sequences of the rat, mouse, and human p75NTR genes. We found that only one of these, a proximal region rich in Sp1 sites, responds to changes in hypo-osmolarity. We then showed that Sp1 DNA binding activity is increased in cells exposed to hypoosmolarity, established that hypo-osmolarity enhanced Sp1 binding to the endogenous p75NTR promoter, and showed that Sp1 is required for p75NTR expression induced by hypo-osmolarity. We examined how Sp1 is regulated to effect these changes and established that Sp1 turnover is strongly inhibited by hypo-osmolarity. We propose that stress-induced Sp1 accumulation that results from reductions in Sp1 turnover rate contributes to injury-induced gene expression.

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“…This increase was completely blocked by both concentrations of ATRA when compared to OGD (p<0.05; Figure 3A and B). ] i induced cell swelling in lactacidosis-induced glial swelling [43,44], and hypo-osmotic swelling in cultured astrocytes [45]. To examine whether ATRA regulates [Ca2+] i , we assessed changes in …”

Section: Cell Volume Determinationmentioning

confidence: 99%

Acute effects of all-trans-retinoic acid in ischemic injury

Panickar¹,

Dawson

2012

Translational Neuroscience

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All-trans-retinoic acid (ATRA) is a vitamin A derivative that is important in neuronal patterning, survival, and neurite outgrowth. Neuroprotective effects of ATRA in ischemia have been demonstrated but its effects on glial swelling are not known. We investigated the relatively acute effects of ATRA on cell swelling in ischemic injury and on key features hypothesized to contribute to cell swelling including increased reactive oxygen species/ reactive nitrogen species (ROS/RNS), depolarization of the inner mitochondrial membrane potential (ΔΨ m ), and increased intracellular calcium ([Ca 2+ ] i ). C6 glial cultures were subjected to 5 hr oxygen-glucose deprivation (OGD). ATRA was added to separate groups after the end of OGD. OGD increased cell volume by 43%, determined at 90 min after the end of OGD, but this increase was significantly attenuated by ATRA. OGD induced an increase in ROS/RNS production in the whole cell and mitochondria, as assessed by the fluorescent dyes CM-H 2 DCFDA and MitoTracker CM-H 2 -XROS at the end of OGD. The increase in mitochondrial ROS, but not cellular ROS, was significantly attenuated by ATRA. OGD also induced a 67% decline in mitochondrial ΔΨ m but this decline was significantly attenuated by ATRA. OGD-induced increase in [Ca 2+ ] i was also significantly attenuated by ATRA. Taken together with our previous results where calcium channel blockers reduced cell swelling, the effects of ATRA in attenuating swelling are possibly mediated through its effects in regulating [Ca 2+ ] i . Considering the paucity of agents in attenuating brain edema in ischemia, ATRA has the potential to reduce brain edema and associated neural damage in ischemic injury.

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Characterization of the hypo-osmolarity-induced Ca2+ response in cultured rat astrocytes

Cited by 56 publications

References 31 publications

K_V7/M Channels Mediate Osmotic Modulation of Intrinsic Neuronal Excitability

K_V7/M Channels Mediate Osmotic Modulation of Intrinsic Neuronal Excitability

Hypo-Osmolar Stress Induces p75NTR Expression by Activating Sp1-Dependent Transcription

Acute effects of all-trans-retinoic acid in ischemic injury

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Characterization of the hypo-osmolarity-induced Ca2+ response in cultured rat astrocytes

Cited by 56 publications

References 31 publications

KV7/M Channels Mediate Osmotic Modulation of Intrinsic Neuronal Excitability

KV7/M Channels Mediate Osmotic Modulation of Intrinsic Neuronal Excitability

Hypo-Osmolar Stress Induces p75NTR Expression by Activating Sp1-Dependent Transcription

Acute effects of all-trans-retinoic acid in ischemic injury

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K_V7/M Channels Mediate Osmotic Modulation of Intrinsic Neuronal Excitability

K_V7/M Channels Mediate Osmotic Modulation of Intrinsic Neuronal Excitability