Block of spontaneous termination of paroxysmal depolarizations by forskolin (buccal ganglia, Helix pomatia)

Üre, Atik; Altrup, U.

doi:10.1016/j.neulet.2005.08.045

Cited by 14 publications

(6 citation statements)

References 37 publications

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“…Third, inhibition of PKA by KT 5720 and Rp-cAMPS significantly reduced but not completely blocked CRF-induced increases in epileptiform activity. In accordance with our results, tremendous evidence demonstrates that AC/cAMP/PKA pathway plays a facilitatory role in epilepsy [53], [54], [55], [56], [57], [58].…”

Section: Discussionsupporting

confidence: 93%

“…Because CRF 2 receptors are coupled to AC/cAMP/PKA pathway and there is strong evidence demonstrating that cAMP and PKA signals exert a tonic control of epilepsy [53], [54], [55], [56], [57], [58], we tested the roles of this pathway in CRF-mediated facilitation of epileptiform activity. Slices were pretreated with the selective AC inhibitor MDL 12330A (50 µM) for ∼20 min and the same concentration of MDL 12330A was included in the PTX-containing extracellular solution and applied in the bath before and during the application of CRF.…”

Section: Resultsmentioning

confidence: 99%

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Corticotropin-Releasing Factor Facilitates Epileptiform Activity in the Entorhinal Cortex: Roles of CRF2 Receptors and PKA Pathway

2014

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Whereas corticotropin-releasing factor (CRF) has been considered as the most potent epileptogenic neuropeptide in the brain, its action site and underlying mechanisms in epilepsy have not been determined. Here, we found that the entorhinal cortex (EC) expresses high level of CRF and CRF2 receptors without expression of CRF1 receptors. Bath application of CRF concentration-dependently increased the frequency of picrotoxin (PTX)-induced epileptiform activity recorded from layer III of the EC in entorhinal slices although CRF alone did not elicit epileptiform activity. CRF facilitated the induction of epileptiform activity in the presence of subthreshold concentration of PTX which normally would not elicit epileptiform activity. Bath application of the inhibitor for CRF-binding proteins, CRF6-33, also increased the frequency of PTX-induced epileptiform activity suggesting that endogenously released CRF is involved in epileptogenesis. CRF-induced facilitation of epileptiform activity was mediated via CRF2 receptors because pharmacological antagonism and knockout of CRF2 receptors blocked the facilitatory effects of CRF on epileptiform activity. Application of the adenylyl cyclase (AC) inhibitors blocked CRF-induced facilitation of epileptiform activity and elevation of intracellular cyclic AMP (cAMP) level by application of the AC activators or phosphodiesterase inhibitor increased the frequency of PTX-induced epileptiform activity, demonstrating that CRF-induced increases in epileptiform activity are mediated by an increase in intracellular cAMP. However, application of selective protein kinase A (PKA) inhibitors reduced, not completely blocked CRF-induced enhancement of epileptiform activity suggesting that PKA is only partially required. Our results provide a novel cellular and molecular mechanism whereby CRF modulates epilepsy.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Corticotropin-Releasing Factor Facilitates Epileptiform Activity in the Entorhinal Cortex: Roles of CRF2 Receptors and PKA Pathway

2014

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“…properties (Speckmann and Caspers, 1973;Altrup and Speckmann, 1988;Madeja et al, 1989;Altrup et al, 1991;Schulze-Bonhage et al, 1993;Altrup et al, 2003;Üre and Altrup, 2006;Giachello et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The neurons of Helix land snails have been used frequently to studying the mechanisms underlying drug-induced epileptic-like activity (Speckmann and Caspers, 1973;Altrup and Speckmann, 1988;Madeja et al, 1989;Altrup et al, 1991;Altrup et al, 2003;Altrup et al, 2006;Üre and Altrup, 2006), mimicking those described in mammalian neurons (Chalazonitis and Takeuchi, 1968;Speckmann and Caspers, 1973). More recently the isolated Helix neurons have also been used to study the effects of the drug-induced epileptiform activity on basal synaptic transmission and post-tetanic potentiation .…”

Section: Introductionmentioning

confidence: 99%

Subconvulsant doses of pentylenetetrazol uncover the epileptic phenotype of cultured synapsin-deficient Helix serotonergic neurons in the absence of excitatory and inhibitory inputs

Brenes

Carabelli²,

Gosso³

et al. 2016

Epilepsy Research

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Synapsins are a family of presynaptic proteins related to several processes of synaptic functioning. A variety of reports have linked mutations in synapsin genes with the development of epilepsy. Among the proposed mechanisms, a main one is based on the synapsin-mediated imbalance towards network hyperexcitability due to differential effects on neurotransmitter release in GABAergic and glutamatergic synapses. Along this line, a non-synaptic effect of synapsin depletion increasing neuronal excitability has recently been described in Helix neurons. To further investigate this issue, we examined the effect of synapsin knock-down on the development of pentylenetetrazol (PTZ)-induced epileptic-like activity using single neurons or isolated monosynaptic circuits reconstructed on microelectrode arrays (MEAs). Compared to control neurons, synapsin-silenced neurons showed a lower threshold for the development of epileptic-like activity and prolonged periods of activity, together with the occurrence of spontaneous firing after recurrent PTZ-induced epileptic-like activity. These findings highlight the crucial role of synapsin on neuronal excitability regulation in the absence of inhibitory or excitatory inputs. KeywordsSynapsin; pentylenetetrazol (PTZ); invertebrate neurons; convulsants; Helix snail. Highlights• Synapsin-silenced cells lacking synaptic inputs exhibit greater PTZ susceptibility.• PTZ-induced epileptic-like behaviors were increased in synapsin-silenced cells.• Recurrent epileptic-like activity impairs control neuron synaptogenesis.• Recurrent epileptic-like activity is associated with spontaneous spiking activity.

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“…PKA activity increases in the neocortex and hippocampus of rats during epileptogenesis (Yechikhov et al., 2001). Activation of the cAMP–PKA pathway increases excitability and enhances epileptiform activity in vitro (Boulton et al., 1993; Higashima et al., 2002; Chen & Roper, 2003), and results in a potentiation of epileptic activity and status epilepticus in vivo (Üre & Altrup, 2006). We, therefore, asked whether VPA through an action on PKA activity can modify synaptic plasticity and whether such a mechanism of action can explain its anticonvulsant effect.…”

mentioning

confidence: 99%

Inhibition of long‐term potentiation by valproic acid through modulation of cyclic AMP

Chang¹,

Chandler²,

Williams³

et al. 2010

Epilepsia

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SUMMARYPurpose: Valproic acid (VPA) is widely used clinically in epilepsy, bipolar disorder, and migraine. In experimental models, it has also been shown to have neuroprotective and antiepileptogenic effects. Its mechanisms of action in these diverse conditions are, however, unclear, but there is some evidence indicating an effect of VPA upon protein kinase A (PKA) activity. We, therefore, asked whether VPA modulates cyclic adenosine monophosphate (cAMP)/PKA-dependent synaptic plasticity and whether this mode of action could explain its anticonvulsant effect. Methods: We first tested the effects of VPA on PKAdependent synaptic plasticity at mossy fiber to CA3 synapses in rat hippocampus slices following very highfrequency stimulation or application of the adenylyl cyclase activator forskolin. Using biochemical assays, we then tested whether VPA had a direct effect on PKA activity or an indirect effect through modulating cAMP production. Lastly, VPA and inhibitors of adenylyl cyclase (SQ22536) and PKA (H89) were tested in in vitro models of epileptiform activity induced in hippocampal-entorhinal cortex slices using either pentylenetetrazol (2 mM) or low magnesium.Results: VPA (1 mM) inhibited PKA-dependent long-term potentiation of mossy fiber to CA3 pyramidal cell transmission. However, VPA did not directly modulate PKA activity but rather inhibited the accumulation of cAMP. In acute in vitro seizure models, the anticonvulsant activity of VPA is not mediated through modulation of adenylyl cyclase or PKA. Conclusions: These results indicate that VPA through an action on cAMP accumulation can inhibit synaptic plasticity, but this cannot fully explain its anticonvulsant effect.

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Block of spontaneous termination of paroxysmal depolarizations by forskolin (buccal ganglia, Helix pomatia)

Cited by 14 publications

References 37 publications

Corticotropin-Releasing Factor Facilitates Epileptiform Activity in the Entorhinal Cortex: Roles of CRF2 Receptors and PKA Pathway

Corticotropin-Releasing Factor Facilitates Epileptiform Activity in the Entorhinal Cortex: Roles of CRF2 Receptors and PKA Pathway

Subconvulsant doses of pentylenetetrazol uncover the epileptic phenotype of cultured synapsin-deficient Helix serotonergic neurons in the absence of excitatory and inhibitory inputs

Inhibition of long‐term potentiation by valproic acid through modulation of cyclic AMP

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