Nonspecific effects of the gap junction blocker mefloquine on fast hippocampal network oscillations in the adult rat in vitro

Behrens, Christoph; Haq, Rizwan ul; Liotta, Agustin; Anderson, Marlene; Heinemann, Uwe

doi:10.1016/j.neuroscience.2011.07.015

Cited by 23 publications

(32 citation statements)

References 45 publications

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“…These data allow suggesting that obtained in our study significant overlapping of the protective effects of the CBX and MFQ were mediated mainly by Cx36-channels, possibly, with a minimal participation of Cx26-, Cx32-, Cx43-channels and CBX-mediated side effects (e.g., Ca 2þ waves and Na þ -influx blockades, NMDARs and GABARs inhibition) which, incidentally, also contribute to the protective anti-ischemic effects (Cruikshank et al 2004;Beaumont and Maccaferri, 2011;Behrens et al, 2011).…”

Section: Discussionsupporting

confidence: 69%

See 1 more Smart Citation

Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen–glucose deprivation

Voytenko¹,

Lushnikova²,

Savotchenko³

et al. 2015

Brain Research

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Section: Discussionsupporting

confidence: 69%

“…The pannexin1 and pannexin2 were not sensitive to 25 mM MFQ (Madry et al, 2010). The MFQ side-effects commence to appear at concentrations 10-25 mM and differ of the CBX side-effects (Behrens et al, 2011;Cruikshank et al 2004;Beaumont, Maccaferri, 2011).…”

Section: Discussionmentioning

confidence: 88%

Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen–glucose deprivation

Voytenko¹,

Lushnikova²,

Savotchenko³

et al. 2015

Brain Research

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“…Quinine is known as an inhibitor of potassium channels (Henquin, 1982; Smirnov et al, 1999; Päsler et al, 2007). After mefloquine administration, Behrens et al (2011) observed reduced pyramidal cell firing and prolongation of the afterhyperpolarization following an action potential.…”

Section: Tools For Experimental Modulation Of Gj Transmissionmentioning

confidence: 93%

“…As connexin Cx50 is not expressed in the brain, local injection of quinine into brain structure blocks Cx36-GJs (Srinivas et al, 2001). A quinine derivative, mefloquine, also specific for Cx36- and Cx50-GJs, was shown to be more potent than quinine (Cruikshank et al, 2004; Behrens et al, 2011). However, application of quinine and mefloquine is also not free from non-specific effects.…”

Section: Tools For Experimental Modulation Of Gj Transmissionmentioning

confidence: 99%

The contribution of electrical synapses to field potential oscillations in the hippocampal formation

Posluszny

2014

Front. Neural Circuits

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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.

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“…Recently, (Behrens et al, 2011) utilized a more specific gap junction blocker, mefloquine, which blocks Cx36, Cx43, and Cx50, and observed no effect on SPW or associated ripples. In Cx36 knockout mice, in vivo ripple oscillations were unaltered in terms of power, frequency, or probability of occurrence (Buhl et al, 2003).…”

Section: Gap Junctions Sharp Wave-ripple Complexes and Seizuresmentioning

confidence: 99%

Roles of gap junctions, connexins, and pannexins in epilepsy

et al. 2014

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Enhanced gap junctional communication (GJC) between neurons is considered a major factor underlying the neuronal synchrony driving seizure activity. In addition, the hippocampal sharp wave ripple complexes, associated with learning and seizures, are diminished by GJC blocking agents. Although gap junctional blocking drugs inhibit experimental seizures, they all have other non-specific actions. Besides interneuronal GJC between dendrites, inter-axonal and inter-glial GJC is also considered important for seizure generation. Interestingly, in most studies of cerebral tissue from animal seizure models and from human patients with epilepsy, there is up-regulation of glial, but not neuronal gap junctional mRNA and protein. Significant changes in the expression and post-translational modification of the astrocytic connexin Cx43, and Panx1 were observed in an in vitro Co ++ seizure model, further supporting a role for glia in seizure-genesis, although the reasons for this remain unclear. Further suggesting an involvement of astrocytic GJC in epilepsy, is the fact that the expression of astrocytic Cx mRNAs (Cxs 30 and 43) is several fold higher than that of neuronal Cx mRNAs (Cxs 36 and 45), and the number of glial cells outnumber neuronal cells in mammalian hippocampal and cortical tissue. Pannexin expression is also increased in both animal and human epileptic tissues. Specific Cx43 mimetic peptides, Gap 27 and SLS, inhibit the docking of astrocytic connexin Cx43 proteins from forming intercellular gap junctions (GJs), diminishing spontaneous seizures. Besides GJs, Cx membrane hemichannels in glia and Panx membrane channels in neurons and glia are also inhibited by traditional gap junctional pharmacological blockers. Although there is no doubt that connexin-based GJs and hemichannels, and pannexin-based membrane channels are related to epilepsy, the specific details of how they are involved and how we can modulate their function for therapeutic purposes remain to be elucidated.

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Nonspecific effects of the gap junction blocker mefloquine on fast hippocampal network oscillations in the adult rat in vitro

Cited by 23 publications

References 45 publications

Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen–glucose deprivation

Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen–glucose deprivation

The contribution of electrical synapses to field potential oscillations in the hippocampal formation

Roles of gap junctions, connexins, and pannexins in epilepsy

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