Extrasynaptic GABAA Receptors and Tonic Inhibition in Spinal Cord

Loeza‐Alcocer, Emanuel; Andres, Carmen; Aguilar, Justo; Felix, Ricardo; Delgado‐Lezama, Rodolfo

doi:10.1007/978-1-4939-1426-5_8

Cited by 2 publications

(4 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These receptors are conformed mainly by α 4 , α 5 and α 6 subunits, although sometimes they may contain α 2 and α 3 subunits (Farrant and Nusser, 2005 ). Though all these subunits are also expressed in the spinal cord their function is poorly understood (Persohn et al, 1991 ; Wisden et al, 1991 ; Ma et al, 1993 ; Ruano et al, 2000 ; Mody and Pearce, 2004 ; Petri et al, 2005 ; Delgado-Lezama et al, 2013 ; Andres et al, 2014 ; Loeza-Alcocer et al, 2014 ; Bravo-Hernández et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…We have also provided evidence that motoneurons express a tonic current mediated by α 6 subunit-containing GABA A receptors (Andres et al, 2014 ). Likewise, several immunohistochemical and in situ hybridization studies have shown that α 5 subunit-containing GABA A (α 5 GABA A ) receptors are expressed in motoneurons although its role is presently unknown (Persohn et al, 1991 ; Wisden et al, 1991 ; Ma et al, 1993 ; Ruano et al, 2000 ; Mody and Pearce, 2004 ; Petri et al, 2005 ; Loeza-Alcocer et al, 2014 ). Thus, we hypothesized that α 5 GABA A receptors modulating the excitability of motoneurons play a very important role in motor control.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

Canto-Bustos

Loeza‐Alcocer

Cuellar

et al. 2017

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

Motoneurons, the final common path of the Central Nervous System (CNS), are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we confirmed that extrasynaptic α5 subunit-containing GABAA receptors localize with choline acetyltransferase (ChAT) positive cells, suggesting that these receptors are expressed in turtle motoneurons as previously reported in rodents. In these cells, α5GABAA receptors are activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the monosynaptic reflex (MSR) induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

Canto-Bustos

Loeza‐Alcocer

Cuellar

et al. 2017

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…These receptors mediate tonic inhibition in normal conditions, since they have high affinity for ambient GABA and slow desensitization rate (Farrant & Nusser, 2005). Particularly, extrasynaptic GABA A receptors containing α 5 subunit (α 5 ‐GABA A receptors) are localized in dorsal root ganglia (DRG) and spinal cord (Loeza‐Alcocer, Andrés, Aguilar, Felix, & Delgado‐Lezama, 2014). Converging evidence has suggested a role for α 5 ‐GABA A receptor in the pathophysiology of pain (Bohlhalter, Weinmann, Mohler, & Fritschy, 1996; Lorenzo et al., 2014; Paul, Zeilhofer, & Fritschy, 2012; Perez‐Sanchez et al., 2017; Persohn, Malherbe, & Richards, 1991), either as antinociceptive (Perez‐Sanchez et al., 2017; Xue et al., 2017) or pronociceptive (Bravo‐Hernández et al., 2014, 2016; De la Luz‐Cuellar et al., 2019; Hernández‐Reyes et al., 2019).…”

Section: Introductionmentioning

confidence: 99%

Sex‐dependent pronociceptive role of spinal α₅‐GABA_A receptor and its epigenetic regulation in neuropathic rodents

Franco-Enzástiga

García

Murbartián

et al. 2020

Journal of Neurochemistry

View full text Add to dashboard Cite

Extrasynaptic α5‐subunit containing GABAA (α5‐GABAA) receptors participate in chronic pain. Previously, we reported a sex difference in the action of α5‐GABAA receptors in dysfunctional pain. However, the underlying mechanisms remain unknown. The aim of this study was to examine this sexual dimorphism in neuropathic rodents and the mechanisms involved. Female and male Wistar rats or ICR mice were subjected to nerve injury followed by α5‐GABAA receptor inverse agonist intrathecal administration, L‐655,708. The drug produced an antiallodynic effect in nerve‐injured female rats and mice, and a lower effect in males. We hypothesized that changes in α5‐GABAA receptor, probably influenced by hormonal and epigenetic status, might underlie this sex difference. Thus, we performed qPCR and western blot. Nerve injury increased α5‐GABAA mRNA and protein in female dorsal root ganglia (DRG) and decreased them in DRG and spinal cord of males. To investigate the hormonal influence over α5‐GABAA receptor actions, we performed nerve injury to ovariectomized rats and reconstituted them with 17β‐estradiol (E2). Ovariectomy abrogated L‐655,708 antiallodynic effect and E2 restored it. Ovariectomy decreased α5‐GABAA receptor and estrogen receptor α protein in DRG of neuropathic female rats, while E2 enhanced them. Since DNA methylation might contribute to α5‐GABAA receptor down‐regulation in males, we examined CpG island DNA methylation of α5‐GABAA receptor coding gene through pyrosequencing. Nerve injury increased methylation in male, but not female rats. Pharmacological inhibition of DNA methyltransferases increased α5‐GABAA receptor and enabled L‐655,708 antinociceptive effect in male rats. These results suggest that α5‐GABAA receptor is a suitable target to treat chronic pain in females.

show abstract

Extrasynaptic GABAA Receptors and Tonic Inhibition in Spinal Cord

Cited by 2 publications

References 126 publications

Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

Sex‐dependent pronociceptive role of spinal α₅‐GABA_A receptor and its epigenetic regulation in neuropathic rodents

Contact Info

Product

Resources

About

Extrasynaptic GABAA Receptors and Tonic Inhibition in Spinal Cord

Cited by 2 publications

References 126 publications

Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

Sex‐dependent pronociceptive role of spinal α5‐GABAA receptor and its epigenetic regulation in neuropathic rodents

Contact Info

Product

Resources

About

Sex‐dependent pronociceptive role of spinal α₅‐GABA_A receptor and its epigenetic regulation in neuropathic rodents