Volume-activated Cl− currents in different mammalian non-excitable cell types

Nilius, Bernd; Sehrer, J; Viana, Félix; Greef, Christine De; Raeymaekers, Luc; Eggermont, Jan; Droogmans, Guillaume

doi:10.1007/bf00724520

Cited by 97 publications

(57 citation statements)

References 21 publications

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“…The characteristics of ICl,IR are completely different to typical volume-activated chloride currents. Such currents are activated rapidly by depolarization, display outward rectification, have a halide selectivity sequence of I¦ > Br¦ > Cl¦ and require ATP (Anderson, Sheppard, Berger & Welsh, 1992;Ackerman, Wickman & Clapham, 1994;Nilius et al 1994;Arreola et al 1995Arreola et al , 1996. A number of currents which share common features with ICl,IR, such as the hyperpolarization-activated chloride currents of rat osteoblastic cells (Chesnoy-Marchais & Fritsch, 1994), mandibular duct cells (Komwatana, Dinudom, Young & Cook, 1995), T84 cells (Fritsch & Edelman, 1997) and the ClC_2-induced chloride current do exhibit sensitivity to changes in the external osmolarity.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the hyperpolarization‐activated chloride current in dissociated rat sympathetic neurons

Clark

Jordt

Jentsch

et al. 1998

The Journal of Physiology

106

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Dissociated rat superior cervical ganglion (SCG) neurons have been shown to possess a hyperpolarization‐activated inwardly rectifying chloride current. The current was not altered by changes in external potassium concentration, replacing external cations with NMDG (N‐methyl‐D‐glucamine) or by addition of 10 mM caesium or barium ions. The reversal potential of the current was altered by changing external anions. The anion selectivity of the current was Cl− > Br− > I− > cyclamate. All substituted permeant anions also blocked the current. The current was blocked by DIDS (4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid), 9AC (anthracene‐9‐carboxylic acid) and NPPB (5‐nitro‐2‐(3‐phenylpropylamino)benzoic acid) but was unaffected by SITS (4‐acetamido‐4′‐isothiocyanatostilbene‐2,2′‐disulphonic acid) and niflumic acid. The effective blockers were voltage dependent; DIDS and NPPB were more effective at depolarized potentials while 9AC was more effective at hyperpolarized potentials. The current was enhanced by extracellular acidification and reduced by extracellular alkalinization. Reducing external osmolarity was without effect in conventional whole‐cell recording but enhanced current amplitude in those perforated‐patch recordings where little current was evident in control external solution. The current in SCG neurons was blocked by external cadmium and zinc. ClC‐2 chloride currents expressed in Xenopus oocytes were also sensitive to block by these divalent ions and by DIDS but the sensitivity of ClC‐2 to block by cadmium ions was lower than that of the current in SCG neurons. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) experiments showed the presence of mRNA for ClC‐2 in SCG neurons but not in rat cerebellar granule cells which do not possess a hyperpolarization‐activated Cl− current. The data suggest that ClC‐2 may be functionally expressed in rat SCG neurons. This current may play a role in regulating the internal chloride concentration in these neurons and hence their response to activation of GABAA receptors.1. Dissociated rat superior cervical ganglion (SCG) neurons have been shown to possess a hyperpolarization‐activated inwardly rectifying chloride current. The current was not altered by changes in external potassium concentration, replacing external cations with NMDG (N‐methyl‐D‐glucamine) or by addition of 10 mM caesium or barium ions. The reversal potential of the current was altered by changing external anions. The anion selectivity of the current was Cl− > Br− > I− > cyclamate. All substituted permeant anions also blocked the current.

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Section: Discussionmentioning

confidence: 99%

Characterization of the hyperpolarization‐activated chloride current in dissociated rat sympathetic neurons

Clark

Jordt

Jentsch

et al. 1998

The Journal of Physiology

106

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“…The major problem with these compounds is that they do not discriminate well between VRAC and other Cl − channels. Tamoxifen, which is frequently described as the potent and selective inhibitor of the VRAC, is completely ineffective in neuronal cells and blocks a number of other anion and cation channels [60][61][62]. Other VRAC blockers include 1,9-dideoxyforskolin, niflumic acid, calaxarenes, and phloretin [23,24].…”

Section: Volume-regulated Anion Channels and The Reversed Mode Of Glumentioning

confidence: 99%

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

Mongin

2007

Pathophysiology

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The mechanisms of brain tissue damage in stroke are strongly linked to the phenomenon of excitotoxicity, which is defined as damage or death of neural cells due to excessive activation of receptors for the excitatory neurotransmitters glutamate and aspartate. Under physiological conditions, ionotropic glutamate receptors mediate the processes of excitatory neurotransmission and synaptic plasticity. In ischemia, sustained pathological release of glutamate from neurons and glial cells causes prolonged activation of these receptors, resulting in massive depolarization and cytoplasmic Ca 2+ overload. The NMDA subtype of glutamate receptors is particularly important as it represents the main initial route for the Ca 2+ influx. High cytoplasmic levels of Ca 2+ activate many degradative processes that, depending on the metabolic status, cause immediate or delayed death of neural cells. This traditional view has been expanded by a number of observations that implicate Cl − channels and several types of non-channel transporter proteins, such as the Na + ,K + ,2Cl − cotransporter, Na + /H + exchanger, and Na + /Ca 2+ exchanger, in the development of glutamate toxicity. Some of these ion transporters increase tissue damage by promoting pathological cell swelling and necrotic cell death, while others contribute to a long term accumulation of cytoplasmic Ca 2+ . This brief review is aimed at illustrating how the dysregulation of various ion transport processes combine in a 'perfect storm' that disrupts neural ionic homeostasis and culminates in the irreversible damage and death of neural cells. The clinical relevance of individual transporters as targets for therapeutic intervention in stroke is also briefly discussed.

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“…It has been shown recently that intracellular application of the antiallergic drug, sodium cromoglycate, potently blocks intermediate conductance C1-channels (Reinspecht et al, 1992) and in the same concentration-range also inhibits 5-hydroxytryptamine secretion by mast cells (Hemmerich et al, 1991). Other C1-channel blockers, such as NPPB, also affect both mediator secretion and C1-channel activity in mast cells (Romanin et al, 1991), but they are not very selective and also block other channels (see Nilius et al, 1994c).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of volume‐activated chloride currents in endothelial cells by chromones

Heinke

Szücs

Norris³

et al. 1995

British J Pharmacology

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1 We have studied the effects of the reported chloride channel blocker, sodium cromoglycate, on volume-activated C1-currents in endothelial cells from bovine pulmonary artery by means of the wholecell patch clamp technique. Cl-currents were activated by challenging the cells with a hypotonic extracellular solution of 60% of the normal osmolarity. 2 Half maximal activation of the current at + 95 mV occurred after exposure of the cells for 148 ± 10 s (n = 6) to hypotonic solution (HTS). At the same membrane potential but in the presence of 100 gM sodium cromoglycate (disodium-1,3-bis (2'-carboxylate-chromone-5'-yloxy)-2-hydroxy-propane) activation was delayed (253 ± 25 s, n = 6) and the maximal current amplitude was reduced to 63 7% of the control (n = 13). 3 In comparison, an equimolar concentration of NPPB (5-nitro-2(3-phenyl) propylamino-benzoic acid), another Cl-channel blocker, completely blocked the volume-activated current in less than 20 s. 4 Sodium cromoglycate, applied at the time when the HTS-induced current was completely activated, dose-dependently inhibited this current with a concentration for half maximal inhibition of 310 70 gM. Data for nedocromil sodium were not significantly different from those for sodium cromoglycate. 5 Sodium cromoglycate, loaded into the endothelial cells via the patch pipette in ruptured patches, resulted in a decline of the HTS activated current with a time course that was compatible with diffusion of the compound from the pipette into the cell. Intracellulary applied sodium cromoglycate was also more effective and at 50 gM caused a decrease in the amplitude of the current to 25 ± 6% (n = 10) of the control current. 6 It is concluded that blockade of volume-activated Cl-currents by extracellular sodium cromoglycate may be due to an intracellular action following its permeation across the cell membrane.

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Volume-activated Cl− currents in different mammalian non-excitable cell types

Cited by 97 publications

References 21 publications

Characterization of the hyperpolarization‐activated chloride current in dissociated rat sympathetic neurons

Characterization of the hyperpolarization‐activated chloride current in dissociated rat sympathetic neurons

Disruption of ionic and cell volume homeostasis in cerebral ischemia: The perfect storm

Inhibition of volume‐activated chloride currents in endothelial cells by chromones

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