The inhibitory effect of trimethylamine on the anticonvulsant activities of quinine in the pentylenetetrazole model in rats.
ABSTRACT Quinine specifically blocks connexin 36 (Cx36), one of the proteins that form gap junction channels. Quinine suppressed ictal epileptiform activity in in vitro and in vivo studies without decreasing neuronal excitability. In this study, we considered the possible mechanism of anticonvulsant effects of quinine (1, 250, 500, 1000 and 2000 microM, i.c.v.) in the pentylenetetrazole (PTZ) model of seizure. Thus, we used trimethylamine (TMA) (0.05 microM, 5 microM, 50 microM), a gap junction channel opener, to examine whether it could reverse the effects of quinine in rats. Intracerebroventricular (i.c.v.) injection of quinine affected generalized tonic-clonic seizure (GTCS) induced by PTZ by increments in seizure onset and reducing seizure duration. Additionally, pretreatment with different doses of TMA (i.c.v.) attenuated the anticonvulsant effects of quinine on the latency and duration of GTCS. It can be concluded that quinine possesses anticonvulsant effects via modulation of gap junction channels, which could contribute to the control of GTCS.
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ABSTRACT: Electrical synapses are a type of cellular membrane junction referred to as gap junctions (GJs). They provide a direct way to exchange ions between coupled cells and have been proposed as a structural basis for fast transmission of electrical potentials between neurons in the brain. For this reason GJs have been regarded as an important component within the neuronal networks that underlie synchronous neuronal activity and field potential oscillations. Initially, GJs appeared to play a particularly key role in the generation of high frequency oscillatory patterns in field potentials. In order to assess the scale of neuronal GJs contribution to field potential oscillations in the hippocampal formation, in vivo and in vitro studies are reviewed here. These investigations have shown that blocking the main neuronal GJs, those containing connexin 36 (Cx36-GJs), or knocking out the Cx36 gene affect field potential oscillatory patterns related to awake active behavior (gamma and theta rhythm) but have no effect on high frequency oscillations occurring during silent wake and sleep. Precisely how Cx36-GJs influence population activity of neurons is more complex than previously thought. Analysis of studies on the properties of transmission through GJ channels as well as Cx36-GJs functioning in pairs of coupled neurons provides some explanations of the specific influence of Cx36-GJs on field potential oscillations. It is proposed here that GJ transmission is strongly modulated by the level of neuronal network activity and changing behavioral states. Therefore, contribution of GJs to field potential oscillatory patterns depends on the behavioral state. I propose here a model, based on large body of experimental data gathered in this field by several authors, in which Cx36-GJ transmission especially contributes to oscillations related to active behavior, where it plays a role in filtering and enhancing coherent signals in the network under high-noise conditions. In contrast, oscillations related to silent wake or sleep, especially high frequency oscillations, do not require transmission by neuronal GJs. The reliability of neuronal discharges during those oscillations could be assured by conditions of higher signal-to-noise ratio and some synaptic changes taking place during active behavior.Frontiers in Neural Circuits 01/2014; 8:32. · 2.95 Impact Factor
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ABSTRACT: Gap junctions (GJs) were discovered more than five decades ago, and since that time enormous strides have been made in understanding their structure and function. Despite the voluminous literature concerning the function of GJs, the involvement of these membrane structures in the central mechanisms underlying oscillations and synchrony in the neuronal network is still a matter of intensive debate. This review summarizes what is known concerning the involvement of GJs as electrical synapses in mechanisms underlying the generation of oscillations in theta band. The first part of the chapter discusses the role of GJs in mechanisms of oscillations and synchrony. Following this, in vitro, ex vivo, and in vivo experiments concerning the involvement of GJs in the generation of hippocampal formation theta in rats are reviewed.Brain research bulletin 04/2014; · 2.97 Impact Factor
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ABSTRACT: Quinine has anti-epileptic properties in animals. However, in humans this has not been systematically investigated.Annals of Neurosciences 01/2012; 19(1):14-20.