ATP-evoked increases in intracellular calcium in neurons and glia from the dorsal spinal cord

Mw, Salter; Hicks, J. L.

doi:10.1523/jneurosci.14-03-01563.1994

Cited by 185 publications

(138 citation statements)

References 70 publications

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“…8G). Using fura-2 calcium imaging calibration kit (Invitrogen), we estimated that the resting intracellular Ca 2ϩ of astrocytes is 75 Ϯ 5 nM (n ϭ 24), and 348 Ϯ 30 nM (n ϭ 24) after ATP stimulation, similar to a previous report by Salter and Hicks (1994). Will ATP-induced Ca 2ϩ increase affect the dynamin-independent endocytosis in astrocytes?…”

Section: Atp Regulation Of the Dynamin-independent Endocytosis In Astsupporting

confidence: 78%

Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes

Jiang

Chen

2009

Journal of Neuroscience

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Astrocytes release ATP and glutamate through vesicular exocytosis to mediate neuron-glial interactions. In contrast to exocytosis, the endocytic pathways in astroglial cells are poorly understood. Here, we identify a constitutive endocytic pathway in cultured astrocytes that is dependent on neither clathrin nor dynamin. This dynamin-independent endocytic pathway is regulated by Rab5, an early endosome protein. The endocytosed vesicles show fast transition from early endosomes to late endosomes and lysosomes within a few minutes. Interestingly, this clathrin-and dynamin-independent endocytosis in astrocytes is potently regulated by intracellular Ca 2ϩ . ATP and glutamate greatly enhance the dynamin-independent endocytosis through elevating the intracellular Ca 2ϩ . In addition, amyloid-␤ peptide (A␤) also enhances the dynamin-independent endocytosis by inducing Ca 2ϩ transients in astrocytes. These results demonstrate a novel endocytic pathway in glial cells that is dynamin independent but tightly regulated by intracellular Ca 2ϩ . The regulation by ATP, glutamate, and A␤ suggests an important role of the dynamin-independent endocytosis in both physiological and pathological conditions.

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Section: Atp Regulation Of the Dynamin-independent Endocytosis In Astsupporting

confidence: 78%

Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes

Jiang

Chen

2009

Journal of Neuroscience

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“…Previous in vitro studies have shown that activation of purinergic receptors triggers astrocytic Ca 2+ transients (17)(18)(19). We hypothesized that Ca 2+ signals elicited during edema formation depend-at least in part-on ATP release from swollen astrocytes.…”

Section: Discussionmentioning

confidence: 94%

Critical role of aquaporin-4 (AQP4) in astrocytic Ca ²⁺ signaling events elicited by cerebral edema

Thrane

Rappold

Fujita

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

240

247

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Aquaporin-4 (AQP4) is a primary influx route for water during brain edema formation. Here, we provide evidence that brain swelling triggers Ca 2+ signaling in astrocytes and that deletion of the Aqp4 gene markedly interferes with these events. Using in vivo twophoton imaging, we show that hypoosmotic stress (20% reduction in osmolarity) initiates astrocytic Ca 2+ spikes and that deletion of Aqp4 reduces these signals. The Ca 2+ signals are partly dependent on activation of P2 purinergic receptors, which was judged from the effects of appropriate antagonists applied to cortical slices. Supporting the involvement of purinergic signaling, osmotic stress was found to induce ATP release from cultured astrocytes in an AQP4-dependent manner. Our results suggest that AQP4 not only serves as an influx route for water but also is critical for initiating downstream signaling events that may affect and potentially exacerbate the pathological outcome in clinical conditions associated with brain edema.endfeet | glial | two-photon

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“…Intracellular administration of Src40-49 reduced the NMDAR component of the miniature excitatory post-synaptic currents 20 in cultured dorsal horn neurons (Fig. 1c), neurons in which NMDARs are tonically upregulated by Src 14,21,22 .…”

Section: Constructing a Src-nmdar Uncoupling Peptide For Use In Vivomentioning

confidence: 92%

“…Whole-cell recordings were made from cultured dorsal horn neurons as described 20 . Src (40)(41)(42)(43)(44)(45)(46)(47)(48)(49) or sSrc (40)(41)(42)(43)(44)(45)(46)(47)(48)(49) were added to the intracellular solution for a final concentration of 0.015 mg ml −1 .…”

Section: Electrophysiological Recordingsmentioning

confidence: 99%

Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex

Liu

Gingrich

Vargas‐Caballero

et al. 2008

Nat Med

199

205

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Chronic pain hypersensitivity depends upon N-methyl-D-aspartate receptors (NMDARs). However, clinical use of NMDAR blockers is limited by side effects from suppressing physiological functions of these receptors. Here we report a means to suppress pain hypersensitivity without blocking NMDARs but rather by inhibiting the binding of a key enhancer of NMDAR function, the protein tyrosine kinase Src. We show that a peptide consisting of amino acids 40-49 of Src fused to the protein transduction domain of the HIV Tat protein (Src40-49Tat) prevented pain behaviors induced by intraplantar formalin and reversed pain hypersensitivity produced by intraplantar injection of complete Freund's adjuvant or by peripheral nerve injury. Src40-49Tat had no effect on basal sensory thresholds, acute nociceptive responses, or cardiovascular, respiratory, locomotor or cognitive functions. Thus, by targeting Src-mediated enhancement of NMDARs, inflammatory and neuropathic pain are suppressed without deleterious consequences of directly blocking NMDARs, an approach that may be of broad relevance to managing chronic pain.Chronic pain is categorized as inflammatory or neuropathic, each involving neuroplastic changes leading to hypersensitivity in peripheral and central nociceptive systems 1,2 . Multiple mechanisms including increased primary afferent excitability 3 , enhanced transmission in the dorsal horn 1 , changes in gene expression 4 , aberrant neuron-glia interactions 5,6 and neuronal apoptosis 7 are implicated in hypersensitivity in chronic pain models. Abundant pre-clinical evidence indicates that N-methyl-D-aspartate receptor (NMDARs) 8 are critically involved in pain hypersensitivity 9-11 . However, pharmacological blockade of these receptors in humans is deleterious because the activity of NMDARs is essential for many important physiological functions including breathing and locomotion 9,12,13 . A crucial signaling event for NMDAR-dependent neuroplasticity, including pain hypersensitivity 1,14 , is upregulation of NMDAR currents by mechanisms including relieving Mg 2+ blockade and receptor phosphorylation 15,16 . Thus, preferentially inhibiting mechanisms which upregulate NMDARs without affecting basal channel activity represents a strategy that may suppress pain hypersensitivity without impairing key physiological functions.

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ATP-evoked increases in intracellular calcium in neurons and glia from the dorsal spinal cord

Cited by 185 publications

References 70 publications

Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes

Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes

Critical role of aquaporin-4 (AQP4) in astrocytic Ca ²⁺ signaling events elicited by cerebral edema

Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex

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ATP-evoked increases in intracellular calcium in neurons and glia from the dorsal spinal cord

Cited by 185 publications

References 70 publications

Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes

Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes

Critical role of aquaporin-4 (AQP4) in astrocytic Ca 2+ signaling events elicited by cerebral edema

Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex

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Critical role of aquaporin-4 (AQP4) in astrocytic Ca ²⁺ signaling events elicited by cerebral edema