Electrophysiological properties of newborn and adult rat spinal cord glycine receptors expressed in Xenopus oocytes.

Morales, Andrés; Nguyen, Quoc-Thang; Miledi, Ricardo

doi:10.1073/pnas.91.8.3097

Cited by 19 publications

(19 citation statements)

References 25 publications

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“…These newly described NAcc receptors exhibited a set of properties reminiscent of strychnine-sensitive glycine receptors. Thus, NAcc glycine-evoked currents rectified outwardly in both the hyperpolarizing and depolarizing range, a phenomenon observed at voltages negative to Ϫ50 mV in cultured (Bormann et al, 1987;Barry, 1992, 1993) and acutely isolated hypothalamic (Akaike and Kaneda, 1989) neurons, as well as in recombinant glycine receptors in expression systems (Gundersen et al, 1984;Akagi et al, 1991;Morales et al, 1994). The affinity of glycine for NAcc glycine-like receptors was 110 M, a value similar to those obtained from glycine receptors in hyothalamic, cerebellar, and ventral cochlear neurons (Akaike and Kaneda, 1989;Virginio and Cherubini, 1997;Harty and Manis, 1998).…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological Evidence for Expression of Glycine Receptors in Freshly Isolated Neurons from Nucleus Accumbens

Martin

Siggins²

2002

J Pharmacol Exp Ther

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In the course of studying N-methyl-D-aspartate (NMDA) receptors of the nucleus accumbens (NAcc), we found that 20% of freshly isolated medium spiny neurons, as well as all interneurons, responded in an unexpected way to long (5-s) coapplication of NMDA and glycine, the coagonist of NMDA receptors. Whereas the reversal potential of the peak NMDA current of this subset of neurons was still around 0 mV, the desensitizing current became outward at hyperpolarized potentials around Ϫ30 mV. A Cl Ϫ -free solution shifted the equilibrium potentials of the desensitized currents to around 0 mV. This outward current was not blocked by a Ca 2ϩ -free, Ba 2ϩ -containing solution, suggesting that the anionic conductance was not activated by Ca 2ϩ influx through NMDA receptor channels. Interestingly, glycine alone also evoked a current with a similar hyperpolarized reversal potential in this subset of neurons. The glycine current reversed around Ϫ50 mV, rectified outwardly, and inactivated strongly. Its desensitization was best fitted with a double exponential. Only the slow desensitization showed clear voltage dependence. The glycine current was not blocked by 200 M picrotoxin and 10 M zinc, was weakly antagonized by 1 M strychnine, and was not enhanced by 1 M zinc. In addition, 1 mM taurine, but not GABA, inactivated glycine currents, and 1 mM glycine occluded 10 mM taurine-mediated currents. These data indicate that a subset of nucleus accumbens neurons expresses glycine receptors and that either glycine or taurine could be an endogenous agonist for these receptors.The nucleus accumbens (NAcc), an interface region between limbic structures (hippocampus, amygdala, and prefrontal cortex) and the extrapyramidal motor system, modulates cognitive and motivational aspects of behavior that are translated into motor activity (Dunah et al., 1996). Projecting GABAergic neurons, also containing mostly either substance P or enkephalin, account for 90% of the neuronal population of NAcc (Meredith, 1999). These neurons receive massive dopaminergic input from the ventral tegmental area, glutamatergic input from cortical and subcortical regions, and GABA innervation from interneurons. The physiology of the receptors for these transmitters is relatively well known, because they have been heavily studied with regard to addiction to psychostimulants, opiates, and alcohol (Koob et al., 1998). NAcc-projecting neurons also receive inputs from acetylcholine-and somatostatin-containing interneurons (Groenewegen et al., 1991;Meredith, 1999), but relatively little is known about the physiology of receptors for these ligands in NAcc. Furthermore, some data suggest that other receptors, including glycine receptors, remain to be identified and characterized.Glycine receptors, along with GABA receptors, represent the primary fast inhibitory mechanisms in the central nervous system. Activation of glycine receptors opens anionic channels that hyperpolarize neurons. Until recently, it was generally believed that glycine receptors were almost exclusiv...

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Section: Discussionmentioning

confidence: 99%

Electrophysiological Evidence for Expression of Glycine Receptors in Freshly Isolated Neurons from Nucleus Accumbens

Martin

Siggins²

2002

J Pharmacol Exp Ther

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“…18), similar to GlyRs expressed by bovine retina and rat spinal cord mRNAs (19,20). The current-voltage relationships were nearly linear from Ϫ50 to ϩ50 mV, but displayed a clear outward rectification at hyperpolarizing potentials attributable to a decrease in the channel open-time (16,20). These results indicate that Cl Ϫ is the main anion flowing through the channels gated by the receptors expressed by the three mRNAs.…”

Section: Expression Of Gly and Gaba Receptors By Embryonic Brain Mrnasmentioning

confidence: 51%

“…3), and in all cases the Gly-current reversal potential was close to the Cl Ϫ equilibrium potential (Ϫ30 mV; ref. 18), similar to GlyRs expressed by bovine retina and rat spinal cord mRNAs (19,20). The current-voltage relationships were nearly linear from Ϫ50 to ϩ50 mV, but displayed a clear outward rectification at hyperpolarizing potentials attributable to a decrease in the channel open-time (16,20).…”

Section: Expression Of Gly and Gaba Receptors By Embryonic Brain Mrnasmentioning

confidence: 91%

Characteristics of glycine receptors expressed by embryonic rat brain mRNAs

Garcı́a-Alcocer¹,

Garcı́a-Colunga²,

Martı́nez-Torres³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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A study was made of glycine (Gly) and ␥-aminobutyric acid (GABA) receptors expressed in Xenopus oocytes injected with rat mRNAs isolated from the encephalon, midbrain, and brainstem of 18-dayold rat embryos. In oocytes injected with encephalon, midbrain, or brainstem mRNAs, the Gly-current amplitudes (membrane current elicited by Gly; 1 mM Gly) were respectively 115 ؎ 35, 346 ؎ 28, and 389 ؎ 22 nA, whereas the GABA-currents (1 mM GABA) were all <40 nA. Moreover, the Gly-currents desensitized faster in oocytes injected with encephalon or brainstem mRNAs. The EC 50 for Gly was 611 ؎ 77 M for encephalon, 661 ؎ 28 M for midbrain, and 506 ؎ 18 M for brainstem mRNA-injected oocytes, and the corresponding Hill coefficients were all Ϸ2. Strychnine inhibited all of the Gly-currents, with an IC50 of 56 ؎ 3 nM for encephalon, 97 ؎ 4 nM for midbrain, and 72 ؎ 4 nM for brainstem mRNAs. During repetitive Gly applications, the Gly-currents were potentiated by 1.6-fold for encephalon, 2.1-fold for midbrain, and 1.3-fold for brainstem RNA-injected oocytes. Raising the extracellular Ca 2؉ concentration significantly increased the Gly-currents in oocytes injected with midbrain and brainstem mRNAs. Reverse transcription-PCR studies showed differences in the Gly receptor (GlyR) ␣-subunits expressed, whereas the ␤-subunit was present in all three types of mRNA. These results indicate differential expression of GlyR mRNAs in the brain areas examined, and these mRNAs lead to the expression of GlyRs that have different properties. The modulation of GlyRs by Ca 2؉ could play important functions during brain development.I n all vertebrates the main neurotransmitters responsible for fast inhibitory synaptic transmission are the amino acids glycine (Gly) and ␥-aminobutyric acid (GABA), which act on their specific receptors (1, 2). Molecular cloning indicates that both Gly receptors (GlyR) and GABA receptors (GABAR) have a pentameric subunit structure, arranged around a chloride-selective ion channel. The GlyR is composed of two types of glycosylated integral membrane proteins (␣1-␣4 and ␤) and an associated peripheral membrane protein (1). On the other hand, the GABAR are made up of combinations of ␣-, ␤-, ␥-, ␦-, -, -, or -subunits (3). The density, location, and subunit composition of some neurotransmitter receptors change during development. For example, mammalian fetal skeletal muscle fibers have acetylcholine receptors along their entire surface and the receptors disappear from the nonjunctional areas during development (4), and their subunit composition is also changed (5). Similarly, the amount of GlyR gene translation, assessed by the injection of developing rat cerebral cortex mRNA into Xenopus oocytes, decreases with age, whereas that of GABARs increases (6). Moreover, the type and location of mRNAs coding for GlyR changes ontogenetically (7), and the subunit composition is also changed, because the ␣2-subunit seen by in situ hybridization in embryonic day 14 (E14) midbrain is not found after E19 (8). Additionally, during developm...

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“…This suggests that glycine induces the anion current. 21) Moreover, co-treatment of resveratrol with glycine did not affect the glycine receptor channel property because resveratrol did not change the reversal potential of the glycine receptor (Fig. 4A).…”

Section: Resultsmentioning

confidence: 99%

Resveratrol Inhibits Glycine Receptor-Mediated Ion Currents

Lee

Hwang

Choi

et al. 2014

Biological & Pharmaceutical Bulletin

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Resveratrol is found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-nociceptive, and life-prolonging effects. However, the single cellular mechanisms by which resveratrol acts are relatively unknown, especially in terms of possible regulation of receptors involved in synaptic transmission. The glycine receptor is an inhibitory ligand-gated ion channel involved in fast synaptic transmission in spinal cord. In the present study, we investigated the effect of resveratrol on human glycine receptor channel activity. Glycine α1 receptors were expressed in Xenopus oocytes and glycine receptor channel activity was measured using a two-electrode voltage clamp technique. Treatment with resveratrol alone had no effect on oocytes injected with H 2 O or on oocytes injected with glycine α1 receptor cRNA. In the oocytes injected with glycine α1 receptor cRNA, co-or pretreatment of resveratrol with glycine inhibited the glycine-induced inward peak current (I Gly ) in a reversible manner. The inhibitory effect of resveratrol on I Gly was also concentration dependent, voltage independent, and non-competitive. These results indicate that resveratrol regulates glycine receptor channel activity and that resveratrol-mediated regulation of glycine receptor channel activity is one of several cellular action mechanisms of resveratrol for pain regulation.Key words resveratrol; glycine; glycine receptor; ligand-gated ion channel; Xenopus oocyte Resveratrol is a phytoalexin found in grapes, red wine, and other berries (Fig. 1A) and is also produced as an anti-fungal chemical by plants.1) The concentration of resveratrol in red wine is as high as 0.2-5.8 mg/L.2) Resveratrol exhibits diverse physiological and pharmacological activities, such as anti-cancer, chemopreventive, antiviral, cardio-protective, anti-aging, anti-nociceptive, and life-prolonging effects.2-4) Resveratrol exhibits beneficial effects on the nervous system. It attenuates neurodegenerative disorders such as Alzheimer's disease.5) It also attenuates neuronal cell death from in vitro or in vivo brain hypoxia or ischemic conditions. 6,7) Although accumulating evidence indicates that resveratrol has diverse beneficial properties, including protective effects on the nervous system, relatively little is known about its cellular action, especially with respect to possible regulation of the receptors involved in synaptic transmission.The glycine receptor belongs to the superfamily of ligandgated ion channel receptors that are structurally similar to nicotinic acetylcholine, 5-HT 3 , and γ-aminobutyric acid A (GABA A ) receptors. 8,9) Glycine receptors are dominantly expressed in the spinal cord.10) The physiological roles of glycine receptors in these regions mediate post-synaptic inhibition for reflex responses, voluntary motor control, and the processing of sensory signals, 10) because the glycine receptor forms a chloride-permeable and -selective transmembrane channel. Glycine recep...

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Electrophysiological properties of newborn and adult rat spinal cord glycine receptors expressed in Xenopus oocytes.

Cited by 19 publications

References 25 publications

Electrophysiological Evidence for Expression of Glycine Receptors in Freshly Isolated Neurons from Nucleus Accumbens

Electrophysiological Evidence for Expression of Glycine Receptors in Freshly Isolated Neurons from Nucleus Accumbens

Characteristics of glycine receptors expressed by embryonic rat brain mRNAs

Resveratrol Inhibits Glycine Receptor-Mediated Ion Currents

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