Quinine suppresses extracellular potassium transients and ictal epileptiform activity without decreasing neuronal excitability in vitro

Bikson, Marom; Bihi, Rachid Id; Vreugdenhil, Martin; Köhling, Rüdiger; Fox, J. E. D.; Jefferys, John G. R.

doi:10.1016/s0306-4522(02)00320-2

Cited by 42 publications

(33 citation statements)

References 34 publications

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“…Carbenoxolone inhibits both spontaneous and seizure-like events evoked by a single stimulus and brief titanic stimulation of the Schaffer collaterals, while a connexin-mimetic peptide (Gap 27) attenuates spontaneous recurrent epileptiform activity [96] . In addition, the Cx36-selective blocker quinine markedly reduces the number of spikes in the after-discharges evoked by alvear stimulation in low-Ca 2+ solution [97] .…”

Section: In Vitro Studies Using Gap Junction Blockers Andmentioning

confidence: 96%

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Role of gap junctions in epilepsy

Jin

Chen

2011

Neurosci. Bull.

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Epilepsy is a common neurological disorder characterized by periodic and unpredictable seizures. Gap junctions have recently been proposed to be involved in the generation, synchronization and maintenance of seizure events.The present review mainly summarizes recent reports concerning the contribution of gap junctions to the pathophysiology of epilepsy, together with the regulation of connexin after clinical and experimental seizure activity. The anticonvulsant effects of gap junction blockers both in vitro and in vivo suggest that the gap junction is a candidate target for the development of antiepileptic drugs. It is also of interest that the roles of neuronal and astrocytic gap junctions in epilepsy have been investigated independently, based on evidence from pharmacological manipulations and connexin-knockout mice.Further studies using more specific manipulations of gap junctions in different cell types and in human epileptic tissue are needed to fully uncover the role of gap junctions in epilepsy.

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Section: In Vitro Studies Using Gap Junction Blockers Andmentioning

confidence: 96%

“…After >40 min in quinine, interictal activity in CA3 is abolished, however, very high-frequency 'mini-population spikes' persist [97] . [98] .…”

Section: Continuedmentioning

confidence: 99%

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Role of gap junctions in epilepsy

Jin

Chen

2011

Neurosci. Bull.

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“…5 Studies have demonstrated that quinine suppresses ictal activity without affecting normal neuronal function in both in-vitro (rat hippocampal slice preparation) 7 and in-vivo (4-aminopyridine induced epilepsy model) 3 conditions. Further, trimethylamine, a specific opener of GJ channels negates quinine's seizure protective activity.…”

Section: Discussionmentioning

confidence: 99%

“…5 Various studies have documented in-vitro and in-vivo anticonvulsant activity of quinine in animal models. 3,[6][7][8][9] However, there is a paucity of data wherein the anticonvulsant activity of quinine is compared with drugs currently used in treating epilepsy.…”

Section: Introductionmentioning

confidence: 99%

Anticonvulsant activity of quinine in rat models of seizure in comparison with valproate and phenytoin

Bn¹,

Sinha²,

Joshi³

et al. 2014

J. Young Pharm.

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Background: Presently available anti-seizure drugs cannot control seizures in 20-40% epilepsy patients who develop refractory epilepsy. None of the currently available anti-seizure drugs targets hypersynchronization of epileptogenic impulses. Process of hypersynchronization involves gap junction (GJ) activity. Quinine blocks GJs, and prevents seizures in animal models. Since comparative studies were lacking, this animal study compared anticonvulsant activity of quinine with that of valproate and phenytoin. Materials and Methods: Seizures were induced in adult albino Sprague/Dawley rats (n = 72) using pentylenetetrazole (PTZ) and maximum electroshock (MES) methods, comparator drugs being valproate (90 mg/kg) and phenytoin (27 mg/kg), respectively. Quinine was given in three doses (28, 35 and 42 mg/kg). Results: Higher doses of quinine (35 and 42 mg/kg) controlled PTZ seizures; efficacy was similar to valproate. MES seizures were not suppressed. Conclusion: Quinine has in-vivo anticonvulsant activity in rats in PTZ model at higher doses, but not in MES model in the doses tested.

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Inhibition of Connexin 36 attenuates HMGB1‐mediated depressive‐like behaviors induced by chronic unpredictable mild stress

Jiang

Zeng

et al. 2022

Brain and Behavior

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Background: High mobility group box 1 (HMGB1) released by neurons and microglia was demonstrated to be an important mediator in depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which could lead to the imbalance of two different metabolic approaches in kynurenine pathway (KP), thus enhancing glutamate transmission and exacerbating depressive-like behaviors. Evidence showed that HMGB1 signaling might be regulated by Connexin (Cx) 36 in inflammatory diseases of central nervous system (CNS). Our study aimed to further explore the role of Cx36 in depressive-like behaviors and its relationship with HMGB1.Methods: After 4-week chronic stress, behavioral tests were conducted to evaluate depressive-like behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Western blot analysis and immunofluorescence staining were used to observe the expression and location of Cx36. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the concentrations of inflammatory cytokines. And the excitability and inward currents of hippocampal neurons were recorded by whole-cell patch clamping. Results:The expression of Cx36 was significantly increased in hippocampal neurons of mice exposed to CUMS, while treatment with glycyrrhizinic acid (GZA) or quinine could both down-regulate Cx36 and alleviate depressive-like behaviors. The proinflammatory cytokines like HMGB1, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were all elevated by CUMS, and application of GZA and quinine could decrease them. In addition, the enhanced excitability and inward currents of hippocampal neurons induced by lipopolysaccharide (LPS) could be reduced by either GZA or quinine.Conclusions: Inhibition of Cx36 in hippocampal neurons might attenuates HMGB1mediated depressive-like behaviors induced by CUMS through down-regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload.

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Quinine suppresses extracellular potassium transients and ictal epileptiform activity without decreasing neuronal excitability in vitro

Cited by 42 publications

References 34 publications

Role of gap junctions in epilepsy

Role of gap junctions in epilepsy

Anticonvulsant activity of quinine in rat models of seizure in comparison with valproate and phenytoin

Inhibition of Connexin 36 attenuates HMGB1‐mediated depressive‐like behaviors induced by chronic unpredictable mild stress

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