GABAA receptors mediate motoneuron tonic inhibition in the turtle spinal cord

Castro, Alberto; Aguilar, Justo; Andres, Carmen; Felix, Ricardo; Delgado‐Lezama, Rodolfo

doi:10.1016/j.neuroscience.2011.06.073

Cited by 14 publications

(13 citation statements)

References 39 publications

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“…This increased primary afferent tonic excitability suggests the presence of tonically active GABA A receptors in primary afferents, shunting the electrical stimulus as in mossy fibers (Ruiz et al 2003). Shunting by tonically active GABA A receptors has also been reported in cerebellar granule cells (Chadderton et al 2004) and motoneurons (Castro et al 2011a;Delgado-Lezama et al 2004), where excitatory postsynaptic potentials (Chadderton et al 2004;Delgado-Lezama et al 2004) were facilitated after blockade of extrasynaptic GABA A receptors.…”

Section: Discussionmentioning

confidence: 83%

α₅GABA_A receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord

Loeza‐Alcocer

Canto-Bustos

Aguilar

et al. 2013

Journal of Neurophysiology

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γ-Amino butyric acid (GABA) plays a key role in the regulation of central nervous system by activating synaptic and extrasynaptic GABAA receptors. It is acknowledged that extrasynaptic GABAA receptors located in the soma, dendrites, and axons may be activated tonically by low extracellular GABA concentrations. The activation of these receptors produces a persistent conductance that can hyperpolarize or depolarize nerve cells depending on the Cl(-) equilibrium potential. In an in vitro preparation of the turtle spinal cord we show that extrasynaptic α5GABAA receptors mediate the tonic state of excitability of primary afferents independently of the phasic primary afferent depolarization mediated by synaptic GABAA receptors. Blockade of α5GABAA receptors with the inverse agonist L-655,708 depressed the dorsal root reflex (DRR) without affecting the phasic increase in excitability of primary afferents. Using RT-PCR and Western blotting, we corroborated the presence of the mRNA and the α5GABAA protein in the dorsal root ganglia of the turtle spinal cord. The receptors were localized in primary afferents in dorsal root, dorsal root ganglia, and peripheral nerve terminals using immunoconfocal microscopy. Considering the implications of the DRR in neurogenic inflammation, α5GABAA receptors may serve as potential pharmacological targets for the treatment of pain.

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Section: Discussionmentioning

confidence: 83%

α₅GABA_A receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord

Loeza‐Alcocer

Canto-Bustos

Aguilar

et al. 2013

Journal of Neurophysiology

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“…GABA A Rs are essential for information processing and involved in many pathological processes such as epilepsy, pain, and anxiety (Semyanov et al, 2004). GABA A Rs mediate both phasic and tonic inhibition in neurons from hippocampus, cerebellum, thalamus, and sensory cortex (Castro et al, 2011). Whereas synaptic GABA A Rs are involved in phasic inhibition responding to GABA release from interneurons, extrasynaptic GABA A Rs are responsible for the generation of tonic inhibition (Brickley et al, 1996;Bright and Brickley, 2008;Farrant and Nusser, 2005;Mody, 2001;Nusser and Mody, 2002;Wall and Usowicz, 1997).…”

Section: Introductionmentioning

confidence: 99%

Alpha-asarone from Acorus gramineus alleviates epilepsy by modulating A-Type GABA receptors

Huang

Zhang

et al. 2013

Neuropharmacology

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“…We have also shown that motoneurons display a GABAergic inhibitory tonic current mediated by GABA A receptors activated by ambient GABA, though the type of α subunit(s) in these receptors was not investigated [16] . Given that furosemide increased the excitability of motoneurons ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Likewise, we have shown that motoneurons exhibit a GABAergic tonic inhibitory current activated by ambient GABA, though the identity of the α subunit(s) in these receptors is presently unknown [16] . Hence, the main aim of this study was to investigate whether furosemide-sensitive α 6 subunit-containing GABA A receptors are expressed in motoneurons and mediate tonic inhibition.…”

Section: Introductionmentioning

confidence: 97%

Extrasynaptic α6 Subunit-Containing GABAA Receptors Modulate Excitability in Turtle Spinal Motoneurons

et al. 2014

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Motoneurons are furnished with a vast repertoire of ionotropic and metabotropic receptors as well as ion channels responsible for maintaining the resting membrane potential and involved in the regulation of the mechanisms underlying its membrane excitability and firing properties. Among them, the GABAA receptors, which respond to GABA binding by allowing the flow of Cl− ions across the membrane, mediate two distinct forms of inhibition in the mature nervous system, phasic and tonic, upon activation of synaptic or extrasynaptic receptors, respectively. In a previous work we showed that furosemide facilitates the monosynaptic reflex without affecting the dorsal root potential. Our data also revealed a tonic inhibition mediated by GABAA receptors activated in motoneurons by ambient GABA. These data suggested that the high affinity GABAA extrasynaptic receptors may have an important role in motor control, though the molecular nature of these receptors was not determined. By combining electrophysiological, immunofluorescence and molecular biology techniques with pharmacological tools here we show that GABAA receptors containing the α6 subunit are expressed in adult turtle spinal motoneurons and can function as extrasynaptic receptors responsible for tonic inhibition. These results expand our understanding of the role of GABAA receptors in motoneuron tonic inhibition.

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GABAA receptors mediate motoneuron tonic inhibition in the turtle spinal cord

Cited by 14 publications

References 39 publications

α₅GABA_A receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord

α₅GABA_A receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord

Alpha-asarone from Acorus gramineus alleviates epilepsy by modulating A-Type GABA receptors

Extrasynaptic α6 Subunit-Containing GABAA Receptors Modulate Excitability in Turtle Spinal Motoneurons

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GABAA receptors mediate motoneuron tonic inhibition in the turtle spinal cord

Cited by 14 publications

References 39 publications

α5GABAA receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord

α5GABAA receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord

Alpha-asarone from Acorus gramineus alleviates epilepsy by modulating A-Type GABA receptors

Extrasynaptic α6 Subunit-Containing GABAA Receptors Modulate Excitability in Turtle Spinal Motoneurons

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α₅GABA_A receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord

α₅GABA_A receptors mediate primary afferent fiber tonic excitability in the turtle spinal cord