On the Role of Voltage-Dependent Calcium Channels in Calcium Signaling of Astrocytes<i>In Situ</i>

Carmignoto, Giorgio; Pasti, Lucia; Pozzan, Tullio

doi:10.1523/jneurosci.18-12-04637.1998

Cited by 153 publications

(92 citation statements)

References 47 publications

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“…In olfactory bulb astrocytes, GABA A receptors appear not to play a predominant role in Ca 2ϩ signaling, which is in contrast to hippocampal astrocytes (11). The presence of voltagegated Ca 2ϩ channels in astrocytes is controversial, since Carmignoto et al (38) failed to detect voltage-dependent Ca 2ϩ signaling in hippocampal astrocytes. In olfactory bulb astrocytes, voltagegated Ca 2ϩ channels appear not to play a major role in Ca 2ϩ signaling, since high K ϩ evoked much smaller Ca 2ϩ transients in astrocytes as compared to neurons (Fig.…”

Section: Discussionmentioning

confidence: 98%

GABA uptake-dependent Ca ²⁺ signaling in developing olfactory bulb astrocytes

Doengi

Hirnet

Coulon

et al. 2009

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

108

105

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2؉ signaling in astrocytes for control of blood flow is demonstrated by SNAP 5114-sensitive constriction of blood vessels accompanying GABA uptake. The results suggest that GABAergic signaling is composed of GABA uptake-mediated Na ؉ rises that reduce Na ؉ /Ca 2؉ exchange, thereby leading to a Ca 2؉ increase sufficient to trigger Ca 2؉ -induced Ca 2؉ release via InsP3 receptors. Hence, GABA transporters not only remove GABA from the extracellular space, but may also contribute to intracellular signaling and astrocyte function, such as control of blood flow.calcium-induced calcium release ͉ GABA transporter ͉ Neuron-glia interaction ͉ sodium imaging ͉ vasoconstriction

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Section: Discussionmentioning

confidence: 98%

GABA uptake-dependent Ca ²⁺ signaling in developing olfactory bulb astrocytes

Doengi

Hirnet

Coulon

et al. 2009

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

108

105

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“…Even in gliogenicinduced seizures, excessive neuronal activity is associated with increases in interstitial K + , decreases in Ca 2+ , and additional glutamate release. High K + , low Ca 2+ , and glutamate 21,38,42 are all potent triggers of astrocytic Ca 2+ signaling and may be independent of etiology of the seizure due to secondary astrocytic activation. Synaptic mechanisms can on the other hand also amplify or generalize a local seizure focus 4 .…”

Section: Discussionmentioning

confidence: 99%

An astrocytic basis of epilepsy

Tian

Azmi²,

Takano

et al. 2005

Nat Med

723

639

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Hypersynchronous neuronal firing is a hallmark of epilepsy, but the mechanisms underlying simultaneous activation of multiple neurons remains unknown. Epileptic discharges are in part initiated by a local depolarization shift that drives groups of neurons into synchronous bursting. In an attempt to define the cellular basis for hypersynchronous bursting activity, we studied the occurrence of paroxysmal depolarization shifts after suppressing synaptic activity by TTX and voltage-gated Ca 2+ channel blockers. Here we report that paroxysmal depolarization shifts can be initiated by release of glutamate from extrasynaptic sources or by photolysis of caged Ca 2+ in astrocytes. Two-photon imaging of live exposed cortex revealed that several anti-epileptics, including valproate, gabapentin and phenytoin, reduced the ability of astrocytes to transmit Ca 2+ signaling. Our results reveal an unanticipated key role for astrocytes in seizure activity. As such, these findings identify astrocytes as a proximal target for the treatment of epileptic disorders.Epilepsy is a neurological disorder in which normal brain function is disrupted as a consequence of intensive burst activity from groups of neurons1. Epilepsies result from long-lasting plastic changes in the brain affecting the expression of receptors and channels, and involve sprouting and reorganization of synapses, as well as reactive gliosis2 ,3 . Several lines of evidence suggest a key role of glutamate in the pathogenesis of epilepsy. Local or systemic administration of glutamate agonists triggers excessive neuronal firing, whereas glutamate receptor (GluR) antagonists have anticonvulsant properties 4 . The observation that astrocytes release glutamate via a regulated Ca 2+ dependent mechanism 5-8 prompted us to hypothesize that glutamate released by astrocytes plays a causal role in synchronous firing of large populations of neurons.Paroxysmal depolarization shifts (PDSs) are abnormal prolonged depolarizations with repetitive spiking and are reflected as interictal discharges in the electroencephalogram 2, 3. We report here that glutamate released by astrocytes can trigger PDSs in several models of experimental seizure. A unifying feature of seizure activity was its consistent association Corresponding author: Guo-Feng Tian (Guo-Feng_Tian@URMC.Rochester.edu). * These authors contributed equally to this work. NIH Public Access RESULTS PDSs can be triggered by an action potential-independent mechanismTo examine the cellular mechanism underlying PDSs, we patched CA1 pyramidal neurons in rat hippocampal slices exposed to 4-aminopyridine (4-AP). 4-AP is a K + channel blocker that induces intense electrical discharges in slices9 and seizure activity in experimental animals 10 . All slices exposed to 4-AP (61 slices from 23 rats) exhibited epileptiform bursting activity expressed as transient episodes of neuronal depolarizations eliciting trains of action potentials (Fig. 1a). Bath application of TTX promptly eliminated neuronal firing (Fig. 1b). Unexpectedly, the...

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“…We decided to explore the molecular nature of voltage-gated Ca 2ϩ channels in cultured astrocytes because expression of these channels in astrocytes has been subject to controversy (Carmignoto et al, 1998). While it has been argued that specific culture conditions such as certain types of sera, cocultures with neurons, or treatment with cAMP substantially influence the expression of voltage-gated Ca 2ϩ channels in astrocytes (Barres et al, 1989;Verkhratsky et al, 1998), high-and low-voltage-activated Ca 2ϩ currents have been recorded from immature astrocytes in hippocampal slices (Akopian et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Expression of voltage‐gated Ca²⁺ channel subtypes in cultured astrocytes

Latour

Hamid

Beedle

et al. 2003

Glia

120

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Transient intracellular [Ca 2ϩ ] increases in astrocytes from influx and/or release from internal stores can release glutamate and thereby modulate synaptic transmission in adjacent neurons. Electrophysiological studies have shown that cultured astrocytes express voltage-dependent Ca 2ϩ channels but their molecular identities have remained unexplored. We therefore performed RT-PCR analysis with primers directed to different voltage-gated Ca 2ϩ channel ␣ 1 subunits. In primary cultures of astrocytes, we detected mRNA transcripts for the, and ␣ 1G (T-type), but not ␣ 1A (P/Q-type), voltage-gated Ca 2ϩ channels. We then used antibodies against all of the Ca 2ϩ channel subunits to confirm protein expression, via Western blots, and localization by means of immunocytochemistry. In Western blot analysis, we observed immunoreactive bands corresponding to the appropriate ␣ 1 subunit proteins. Western blots showed an expression pattern similar to PCR results in that we detected proteins for the ␣ 1B (N-type), ␣ 1C (L-type), ␣ 1D (L-type), ␣ 1E (R-type), and ␣ 1G (T-type), but not ␣ 1A (P/Q-type). Using immunocytochemistry, we observed Ca 2ϩ channel expression for these subunits in punctate clusters on plasmamembrane of GFAP-expressing astrocytes. These results confirm that cultured astrocytes express corresponding proteins to several high-and low-threshold Ca 2ϩ channels but not ␣ 1A (P/Q-type). Overall, our data indicate that astrocytes express multiple types of voltage-gated Ca 2ϩ channels, hinting at a complex regulation of Ca 2ϩ homeostasis in glial cells. GLIA 41:347-353, 2003.

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On the Role of Voltage-Dependent Calcium Channels in Calcium Signaling of AstrocytesIn Situ

Abstract: Calcium ions play crucial roles in a large variety of cell functions. The recent proposal that changes in the intracellular calcium concentration ([Ca 2ϩ

Cited by 153 publications

References 47 publications

GABA uptake-dependent Ca ²⁺ signaling in developing olfactory bulb astrocytes

GABA uptake-dependent Ca ²⁺ signaling in developing olfactory bulb astrocytes

An astrocytic basis of epilepsy

Expression of voltage‐gated Ca²⁺ channel subtypes in cultured astrocytes

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On the Role of Voltage-Dependent Calcium Channels in Calcium Signaling of AstrocytesIn Situ

Abstract: Calcium ions play crucial roles in a large variety of cell functions. The recent proposal that changes in the intracellular calcium concentration ([Ca 2ϩ

Cited by 153 publications

References 47 publications

GABA uptake-dependent Ca 2+ signaling in developing olfactory bulb astrocytes

GABA uptake-dependent Ca 2+ signaling in developing olfactory bulb astrocytes

An astrocytic basis of epilepsy

Expression of voltage‐gated Ca2+ channel subtypes in cultured astrocytes

Contact Info

Product

Resources

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GABA uptake-dependent Ca ²⁺ signaling in developing olfactory bulb astrocytes

GABA uptake-dependent Ca ²⁺ signaling in developing olfactory bulb astrocytes

Expression of voltage‐gated Ca²⁺ channel subtypes in cultured astrocytes