Inhibition of regulatory volume decrease in swollen rat primary astrocyte cultures by methylmercury is due to increased amiloride-sensitive Na+ uptake

Vitarella, Domenico; Kimelberg, Harold K.; Aschner, Michael

doi:10.1016/0006-8993(96)00518-5

Cited by 16 publications

(14 citation statements)

References 45 publications

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“…It has been reported that the Hg 2+ increased Na + uptake through epithelial Na + channels in MDCK cells and the NHE in astrocytes [6,21]. Amiloride apparently acts as a blocker for both pathways [39]; submicromolar amiloride will block Na + channels, but >1 μM amiloride also blocks the NHE.…”

Section: Hg 2+ -Sensitive Na + Transport Pathwaysmentioning

confidence: 98%

“…Hg 2+ produces a large increase in Na + uptake [3,4,6,21]. In order to assess the contribution of Na + in our case, we replaced Na + with the impermeant cation NMDG + [6] in both isotonic and hypotonic solutions (S-II, Table 1).…”

Section: Hg 2+ Effects On Ion Transportmentioning

confidence: 99%

“…There are four likely transport pathways that can be altered by Hg 2+ leading to abnormal volume changes: the epithelial Na + channels [6], the NHE [20,21,35], Na + /Cl -, or Na + /K + /2Cl -cotransporters [36,37], and the Na + -K + -ATPase [17,38]. We excluded the contribution from Na + /Cl -or Na + /K + /2Cl -co-transporters, because Hg 2+ inhibits them [36,37].…”

Section: Hg 2+ -Sensitive Na + Transport Pathwaysmentioning

confidence: 99%

“…Hg 2+ -modification of Na + , K + , and Cl -permeability leads to changes in cell volume and loss of the regulatory volume decrease (RVD) [3,7,19,20]. Mercurial inhibition of RVD has been reported for many different cell types including MDCK [6], astrocytes [3,21], and hepatocytes [4,5], although reportedly acting on different pathways in the different cell types. In MDCK cells, the loss of RVD was ascribed to an enhanced conductance for Na + , K + , and Cl - [6], with the loss of K + compensated by the influx of Na + .…”

Section: Introductionmentioning

confidence: 99%

“…This was attributed to the Na + -dependent anion exchange system and K + -Cl -co-transporters. In astrocytes, the inhibition of RVD was attributed to Na + uptake via the Na + /H + exchanger (NHE) [21].…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Effects of Hg2+-induced Changes in Cell Volume

Heo¹,

Meng²,

Sachs³

et al. 2008

Cell Biochem Biophys

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Using a microfluidic volume sensor, we studied the dynamic effects of Hg 2+ on hypotonic stressinduced volume changes in CHO cells. A hypotonic challenge to control cells caused them to swell but did not evoke a significant regulatory volume decrease (RVD). Treatment with 100 μM HgCl 2 caused a substantial increase in the steady-state volume following osmotic stress. Continuous hypotonic challenge following a single 10-min exposure to HgCl 2 produced a biphasic volume increase with a steady-state volume 100% larger than control cells. Repeated hypotonic challenges to cells exposed once to Hg 2+ resulted in a sequential approach to the same steady-state volume. Stimulation after reaching steady state caused a reduction in peak cell volume. Repeated stimulation was different than continuous stimulation resulting in a more rapid approach to steady state. Substituting extracellular Na + with impermeant NMDG + in the hypotonic solution produced a rapid RVD-like volume decrease and eliminated the Hg 2+ -induced excess swelling. The volume decrease in the presence of Hg 2+ was inhibited by tetraethylammonium and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium, blockers of K + and Cl -channels, respectively, suggesting that part of the Hg 2+ effect was increasing NaCl influx over KCl efflux. The presence of multiple phases of steadystate volume and their sensitivity to the stimulation history suggests that factors beyond solute fluxes, such as modification of mechanical stress within the cytoskeleton also plays a role in the response to hypotonic stress.

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Section: Hg 2+ -Sensitive Na + Transport Pathwaysmentioning

confidence: 98%

Section: Hg 2+ Effects On Ion Transportmentioning

confidence: 99%

Section: Hg 2+ -Sensitive Na + Transport Pathwaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dynamic Effects of Hg2+-induced Changes in Cell Volume

Heo¹,

Meng²,

Sachs³

et al. 2008

Cell Biochem Biophys

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Electrical Resistance Method for Measuring Volume Changes in Astrocytes

Aschner¹

1999

Toxicity Assessment Alternatives

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Volume Measurements in Cultured Primary Astrocytes

Aschner¹

2011

Methods in Molecular Biology

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Damage to the central nervous system (CNS) is selective, likely reflecting the intrinsic properties of -individual cell types. Targets of chemical injury are diverse hence assessing neurotoxicity is extremely difficult. Overcoming this obstacle requires a general screen or "marker" for injury that reflects cellular damage. The "marker" must be reliable and represent a biochemical event which broadly reflects cellular stress and damage. One such "marker" is cell swelling; it occurs in response to a diversity of insults, such as physical damage, disease (ischemia, trauma, and hypoxia), and chemicals (methylmercury, lead, 1,3-dinitrobenzene, and triethyltin). In astrocytes, a type of glia, astrocytic swelling can be measured with several methods. Commonly, freshly isolated astrocytes are grown to confluence on coverslips, a period requiring 3 weeks in culture. At this time, astrocytic volume can be measured using either an impedance technique or 3-O-methyl-D-glucose to assess cell volume. This review will briefly detail these methods and provide insight into molecular mechanisms associated with cell swelling and the ensuing regulatory decrease (RVD).

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Inhibition of regulatory volume decrease in swollen rat primary astrocyte cultures by methylmercury is due to increased amiloride-sensitive Na+ uptake

Cited by 16 publications

References 45 publications

Dynamic Effects of Hg2+-induced Changes in Cell Volume

Dynamic Effects of Hg2+-induced Changes in Cell Volume

Electrical Resistance Method for Measuring Volume Changes in Astrocytes

Volume Measurements in Cultured Primary Astrocytes

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