Acidic ATP activates lymphocyte outwardly rectifying chloride channels via a novel pathway

Ma, Heping; Zhou, Zhenqi; Liang, You‐You; Saxena, Sunil; Warnock, David G.

doi:10.1007/s00424-004-1305-2

Cited by 5 publications

(2 citation statements)

References 48 publications

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“…ATP can activate Cl − currents in diverse cell types (Gurung et al., ; Ma, Zhou, Liang, Saxena, & Warnock, ). As shown in Figure , the reversal potential of ATP‐induced current in our rat ventricular fibroblasts is close to the calculated Nernst potential for Cl − , suggesting that this ATP‐induced current is carried mainly by Cl − .…”

Section: Resultsmentioning

confidence: 99%

ATP increases [Ca²⁺]_iand activates a Ca²⁺‐dependent Cl⁻current in rat ventricular fibroblasts

Hatano

Ohya

Imaizumi

et al. 2018

Experimental Physiology

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Effects of ATP on enzymatically isolated rat ventricular fibroblasts maintained in short-term (36-72 h) cell culture were examined. Immunocytochemical staining of these cells revealed that a fibroblast, as opposed to a myofibroblast, phenotype was predominant. ATP, ADP or uridine 5'-triphosphate (UTP) all produced large increases in [Ca ] . Voltage-clamp studies (amphotericin-perforated patch) showed that ATP (1-100 μm) activated an outwardly rectifying current, with a reversal potential very close to the Nernst potential for Cl . In contrast, ADP was much less effective, and UTP produced no detectable current. The non-selective Cl channel blockers niflumic acid, DIDS and NPPB (each at 100 μm), blocked the responses to 100 μm ATP. An agonist for P2Y purinoceptors, 2-MTATP, activated a very similar outwardly rectifying C1 current. The P2Y receptor antagonists, suramin and PPADS (100 μm each), significantly inhibited the Cl current produced by 100 μm ATP. ATP was able to activate this Cl current when [Ca ] was removed, but not when [Ca ] was buffered with BAPTA-AM. In the presence of the phospholipase C inhibitor U73122, this Cl current could not be activated. PCR analysis revealed strong signals for a number of P2Y purinoceptors and for the Ca -activated Cl channel, TMEM16F (also denoted ANO6). In summary, these results demonstrate that activation of P2Y receptors by ATP causes a phospholipase C-dependent increase in [Ca ] , followed by activation of a Ca -dependent Cl current in rat ventricular fibroblasts.

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Section: Resultsmentioning

confidence: 99%

ATP increases [Ca²⁺]_iand activates a Ca²⁺‐dependent Cl⁻current in rat ventricular fibroblasts

Hatano

Ohya

Imaizumi

et al. 2018

Experimental Physiology

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“…Additional studies have demonstrated ATP-induced activation of anion channels in both osmotically swollen and normal cells (26,51,53,56,83,89). In other cells, extracellular ATP does not initiate an anion current but can potentiate such currents activated by hyposmotic swelling (29,90).…”

Section: Discussionmentioning

confidence: 99%

Purinergic activation of anion conductance and osmolyte efflux in cultured rat hippocampal neurons

Li¹,

Olson²

2008

American Journal of Physiology-Cell Physiology

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Li G, Olson JE. Purinergic activation of anion conductance and osmolyte efflux in cultured rat hippocampal neurons. Am J Physiol Cell Physiol 295: C1550 -C1560, 2008. First published October 15, 2008 doi:10.1152/ajpcell.90605.2007.-The majority of mammalian cells demonstrate regulatory volume decrease (RVD) following swelling caused by hyposmotic exposure. A critical signal initiating RVD is activation of nucleotide receptors by ATP. Elevated extracellular ATP in response to cytotoxic cell swelling during pathological conditions also may initiate loss of taurine and other intracellular osmolytes via anion channels. This study characterizes neuronal ATPactivated anion current and explores its role in net loss of amino acid osmolytes. To isolate anion currents, we used CsCl as the major electrolyte in patch electrode and bath solutions and blocked residual cation currents with NiCl 2 and tetraethylammonium. Anion currents were activated by extracellular ATP with a K m of 70 M and increased over fourfold during several minutes of ATP exposure, reaching a maximum after 9.0 min (SD 4.2). The currents were blocked by inhibitors of nucleotide receptors and volume-regulated anion channels (VRAC). Currents showed outward rectification and inactivation at highly depolarizing membrane potentials, characteristics of swelling-activated anion currents. P2X agonists failed to activate the anion current, and an inhibitor of P2X receptors did not block the effect of ATP. Furthermore, current activation was observed with extracellular ADP and 2-(methylthio)adenosine 5Ј-diphosphate, a P2Y 1 receptor-specific agonist. Much less current activation was observed with extracellular UTP, suggesting the response is mediated predominantly by P2Y 1 receptors. ATP caused a dose-dependent loss of taurine and alanine that could be blocked by inhibitors of VRAC. ATP did not inhibit the taurine uptake transporter. Thus extracellular ATP triggers a loss of intracellular organic osmolytes via activation of anion channels. This mechanism may facilitate neuronal volume homeostasis during cytotoxic edema. amino acids; taurine; cell volume EXTRACELLULAR PURINE AND PYRIMIDINE compounds mediate a variety of brain functions by receptor-mediated action. Extracellular ATP and its metabolic products can initiate cellular responses through two types of receptors: P1 receptors, which are highly sensitive to adenosine, and P2 receptors, sensitive to adenine nucleotides. The P2 receptors are further divided into P2X (ligand-gated channels) or P2Y (G protein-coupled receptors) (1,65,66,77). These receptors are widely distributed in the central nervous system and provoke a variety of effects on neurons and on glial cells.

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Cisplatin Activates Volume-Sensitive Like Chloride Channels Via Purinergic Receptor Pathways in Nasopharyngeal Carcinoma Cells

et al. 2014

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Cisplatin-based concomitant chemoradiotherapy is considered as the standard treatment for locally advanced nasopharyngeal carcinoma patients. However, the curative efficacy of cisplatin-based chemotherapy is limited because of the occurrence of cisplatin resistance. Some researches indicate that activating the volume-sensitive Cl(-) channel might be a new strategy for the reduction of cisplatin resistance. However, little is known about the activation pathway of the Cl(-) channels activated by cisplatin. In this study, the cisplatin-activated chloride current was investigated using the whole cell patch-clamp technique in the poorly differentiated nasopharyngeal carcinoma cells (CNE-2Z cells), and the activation pathway of the current was also discussed. The results showed that extracellular application of cisplatin activated a Cl(-) current, showing the properties of significant outward rectification, intracellular ATP dependency, and a selectivity sequence of I(-) > Br(-) > Cl(-) > gluconate, and being inhibited by the Cl(-) channel inhibitors tamoxifen and extracellular ATP. These characteristics are similar to those of the volume-sensitive Cl(-) current in CNE-2Z cells, indicating that cisplatin induces the Cl(-) current by activating the volume-sensitive like chloride channel. The cisplatin-activated current was blocked by suramin (a wide-spectrum purinergic antagonist) and RB2 (a relatively selective P2Y antagonist). In addition, the current was depressed by extracellular application of apyrase. The apoptotic volume decrease induced by cisplatin was also attenuated by RB2. P2Y receptors were expressed in CNE-2Z cells. These results suggest that cisplatin can induce a Cl(-) current by activating volume-sensitive like Cl(-) channels through the P2Y purinoceptor pathway.

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Acidic ATP activates lymphocyte outwardly rectifying chloride channels via a novel pathway

Cited by 5 publications

References 48 publications

ATP increases [Ca²⁺]_iand activates a Ca²⁺‐dependent Cl⁻current in rat ventricular fibroblasts

ATP increases [Ca²⁺]_iand activates a Ca²⁺‐dependent Cl⁻current in rat ventricular fibroblasts

Purinergic activation of anion conductance and osmolyte efflux in cultured rat hippocampal neurons

Cisplatin Activates Volume-Sensitive Like Chloride Channels Via Purinergic Receptor Pathways in Nasopharyngeal Carcinoma Cells

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Acidic ATP activates lymphocyte outwardly rectifying chloride channels via a novel pathway

Cited by 5 publications

References 48 publications

ATP increases [Ca2+]iand activates a Ca2+‐dependent Cl−current in rat ventricular fibroblasts

ATP increases [Ca2+]iand activates a Ca2+‐dependent Cl−current in rat ventricular fibroblasts

Purinergic activation of anion conductance and osmolyte efflux in cultured rat hippocampal neurons

Cisplatin Activates Volume-Sensitive Like Chloride Channels Via Purinergic Receptor Pathways in Nasopharyngeal Carcinoma Cells

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ATP increases [Ca²⁺]_iand activates a Ca²⁺‐dependent Cl⁻current in rat ventricular fibroblasts

ATP increases [Ca²⁺]_iand activates a Ca²⁺‐dependent Cl⁻current in rat ventricular fibroblasts