Eintrag weiter verarbeiten
Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons
Gespeichert in:
| Zeitschriftentitel: | The Journal of Physiology |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | The Journal of Physiology, 552, 2003, 1, S. 73-87 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Li, Yan‐Fang Wu, Long‐Jun Li, Yong Xu, Lin Xu, Tian‐Le Li, Yan‐Fang Wu, Long‐Jun Li, Yong Xu, Lin Xu, Tian‐Le |
|---|---|
| author |
Li, Yan‐Fang Wu, Long‐Jun Li, Yong Xu, Lin Xu, Tian‐Le |
| spellingShingle |
Li, Yan‐Fang Wu, Long‐Jun Li, Yong Xu, Lin Xu, Tian‐Le The Journal of Physiology Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons Physiology |
| author_sort |
li, yan‐fang |
| spelling |
Li, Yan‐Fang Wu, Long‐Jun Li, Yong Xu, Lin Xu, Tian‐Le 0022-3751 1469-7793 Wiley Physiology http://dx.doi.org/10.1113/jphysiol.2003.047324 <jats:p>Many ionotropic receptors are modulated by extracellular H<jats:sup>+</jats:sup>. So far, few studies have directly addressed the role of such modulation at synapses. In the present study, we investigated the effects of changes in extracellular pH on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) as well as glycine‐evoked currents (<jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>) in mechanically dissociated spinal neurons with native synaptic boutons preserved. H<jats:sup>+</jats:sup> modulated both the mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> biphasically, although it activated an amiloride‐sensitive inward current by itself. Decreasing extracellular pH reversibly inhibited the amplitude of the mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>, while increasing external pH reversibly potentiated these parameters. Blockade of acid‐sensing ion channels (ASICs) with amiloride, the selective antagonist of ASICs, or decreasing intracellular pH did not alter the modulatory effect of H<jats:sup>+</jats:sup> on either mIPSCs or <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. H<jats:sup>+</jats:sup> shifted the EC<jats:sub>50</jats:sub> of the glycine concentration‐response curve from 49.3 ± 5.7 μ<jats:sc>m</jats:sc> at external pH 7.4 to 131.5 ± 8.1 μM at pH 5.5, without altering the Cl<jats:sup>−</jats:sup> selectivity of the glycine receptor (GlyR), the Hill coefficient and the maximal <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>, suggesting a competitive inhibition of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> by H<jats:sup>+</jats:sup>. Both Zn<jats:sup>2+</jats:sup> and H<jats:sup>+</jats:sup> inhibited <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. However, H<jats:sup>+</jats:sup> induced no further inhibition of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> in the presence of a saturating concentration of Zn<jats:sup>2+</jats:sup>. In addition, H<jats:sup>+</jats:sup> significantly affected the kinetics of glycinergic mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. It is proposed that H<jats:sup>+</jats:sup> and/or Zn<jats:sup>2+</jats:sup> compete with glycine binding and inhibit the amplitude of glycinergic mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. Moreover, binding of H<jats:sup>+</jats:sup> induces a global conformational change in GlyR, which closes the GlyR Cl<jats:sup>−</jats:sup> channel and results in the acceleration of the seeming desensitization of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> as well as speeding up the decay time constant of glycinergic mIPSCs. However, the deprotonation rate is faster than the unbinding rate of glycine from the GlyR, leading to reactivation of the undesensitized GlyR after washout of agonist and the appearance of a rebound <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. H<jats:sup>+</jats:sup> also modulated the glycine cotransmitter, GABA‐activated current (<jats:italic>I</jats:italic><jats:sub>GABA</jats:sub>). Taken together, the results support a ‘conformational coupling’ model for H<jats:sup>+</jats:sup> modulation of the GlyR and suggest that H<jats:sup>+</jats:sup> may act as a novel modulator for inhibitory neurotransmission in the mammalian spinal cord.</jats:p> Mechanisms of H<sup>+</sup> Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons The Journal of Physiology |
| doi_str_mv |
10.1113/jphysiol.2003.047324 |
| facet_avail |
Online Free |
| finc_class_facet |
Biologie |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMy9qcGh5c2lvbC4yMDAzLjA0NzMyNA |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMy9qcGh5c2lvbC4yMDAzLjA0NzMyNA |
| institution |
DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 |
| imprint |
Wiley, 2003 |
| imprint_str_mv |
Wiley, 2003 |
| issn |
0022-3751 1469-7793 |
| issn_str_mv |
0022-3751 1469-7793 |
| language |
English |
| mega_collection |
Wiley (CrossRef) |
| match_str |
li2003mechanismsofhmodulationofglycinergicresponseinratsacraldorsalcommissuralneurons |
| publishDateSort |
2003 |
| publisher |
Wiley |
| recordtype |
ai |
| record_format |
ai |
| series |
The Journal of Physiology |
| source_id |
49 |
| title |
Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_unstemmed |
Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_full |
Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_fullStr |
Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_full_unstemmed |
Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_short |
Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_sort |
mechanisms of h<sup>+</sup> modulation of glycinergic response in rat sacral dorsal commissural neurons |
| topic |
Physiology |
| url |
http://dx.doi.org/10.1113/jphysiol.2003.047324 |
| publishDate |
2003 |
| physical |
73-87 |
| description |
<jats:p>Many ionotropic receptors are modulated by extracellular H<jats:sup>+</jats:sup>. So far, few studies have directly addressed the role of such modulation at synapses. In the present study, we investigated the effects of changes in extracellular pH on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) as well as glycine‐evoked currents (<jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>) in mechanically dissociated spinal neurons with native synaptic boutons preserved. H<jats:sup>+</jats:sup> modulated both the mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> biphasically, although it activated an amiloride‐sensitive inward current by itself. Decreasing extracellular pH reversibly inhibited the amplitude of the mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>, while increasing external pH reversibly potentiated these parameters. Blockade of acid‐sensing ion channels (ASICs) with amiloride, the selective antagonist of ASICs, or decreasing intracellular pH did not alter the modulatory effect of H<jats:sup>+</jats:sup> on either mIPSCs or <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. H<jats:sup>+</jats:sup> shifted the EC<jats:sub>50</jats:sub> of the glycine concentration‐response curve from 49.3 ± 5.7 μ<jats:sc>m</jats:sc> at external pH 7.4 to 131.5 ± 8.1 μM at pH 5.5, without altering the Cl<jats:sup>−</jats:sup> selectivity of the glycine receptor (GlyR), the Hill coefficient and the maximal <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>, suggesting a competitive inhibition of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> by H<jats:sup>+</jats:sup>. Both Zn<jats:sup>2+</jats:sup> and H<jats:sup>+</jats:sup> inhibited <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. However, H<jats:sup>+</jats:sup> induced no further inhibition of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> in the presence of a saturating concentration of Zn<jats:sup>2+</jats:sup>. In addition, H<jats:sup>+</jats:sup> significantly affected the kinetics of glycinergic mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. It is proposed that H<jats:sup>+</jats:sup> and/or Zn<jats:sup>2+</jats:sup> compete with glycine binding and inhibit the amplitude of glycinergic mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. Moreover, binding of H<jats:sup>+</jats:sup> induces a global conformational change in GlyR, which closes the GlyR Cl<jats:sup>−</jats:sup> channel and results in the acceleration of the seeming desensitization of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> as well as speeding up the decay time constant of glycinergic mIPSCs. However, the deprotonation rate is faster than the unbinding rate of glycine from the GlyR, leading to reactivation of the undesensitized GlyR after washout of agonist and the appearance of a rebound <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. H<jats:sup>+</jats:sup> also modulated the glycine cotransmitter, GABA‐activated current (<jats:italic>I</jats:italic><jats:sub>GABA</jats:sub>). Taken together, the results support a ‘conformational coupling’ model for H<jats:sup>+</jats:sup> modulation of the GlyR and suggest that H<jats:sup>+</jats:sup> may act as a novel modulator for inhibitory neurotransmission in the mammalian spinal cord.</jats:p> |
| container_issue |
1 |
| container_start_page |
73 |
| container_title |
The Journal of Physiology |
| container_volume |
552 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792335832337612805 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T14:50:48.484Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Mechanisms+of+H%2B+Modulation+of+Glycinergic+Response+in+Rat+Sacral+Dorsal+Commissural+Neurons&rft.date=2003-10-01&genre=article&issn=1469-7793&volume=552&issue=1&spage=73&epage=87&pages=73-87&jtitle=The+Journal+of+Physiology&atitle=Mechanisms+of+H%3Csup%3E%2B%3C%2Fsup%3E+Modulation+of+Glycinergic+Response+in+Rat+Sacral+Dorsal+Commissural+Neurons&aulast=Xu&aufirst=Tian%E2%80%90Le&rft_id=info%3Adoi%2F10.1113%2Fjphysiol.2003.047324&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792335832337612805 |
| author | Li, Yan‐Fang, Wu, Long‐Jun, Li, Yong, Xu, Lin, Xu, Tian‐Le |
| author_facet | Li, Yan‐Fang, Wu, Long‐Jun, Li, Yong, Xu, Lin, Xu, Tian‐Le, Li, Yan‐Fang, Wu, Long‐Jun, Li, Yong, Xu, Lin, Xu, Tian‐Le |
| author_sort | li, yan‐fang |
| container_issue | 1 |
| container_start_page | 73 |
| container_title | The Journal of Physiology |
| container_volume | 552 |
| description | <jats:p>Many ionotropic receptors are modulated by extracellular H<jats:sup>+</jats:sup>. So far, few studies have directly addressed the role of such modulation at synapses. In the present study, we investigated the effects of changes in extracellular pH on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) as well as glycine‐evoked currents (<jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>) in mechanically dissociated spinal neurons with native synaptic boutons preserved. H<jats:sup>+</jats:sup> modulated both the mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> biphasically, although it activated an amiloride‐sensitive inward current by itself. Decreasing extracellular pH reversibly inhibited the amplitude of the mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>, while increasing external pH reversibly potentiated these parameters. Blockade of acid‐sensing ion channels (ASICs) with amiloride, the selective antagonist of ASICs, or decreasing intracellular pH did not alter the modulatory effect of H<jats:sup>+</jats:sup> on either mIPSCs or <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. H<jats:sup>+</jats:sup> shifted the EC<jats:sub>50</jats:sub> of the glycine concentration‐response curve from 49.3 ± 5.7 μ<jats:sc>m</jats:sc> at external pH 7.4 to 131.5 ± 8.1 μM at pH 5.5, without altering the Cl<jats:sup>−</jats:sup> selectivity of the glycine receptor (GlyR), the Hill coefficient and the maximal <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>, suggesting a competitive inhibition of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> by H<jats:sup>+</jats:sup>. Both Zn<jats:sup>2+</jats:sup> and H<jats:sup>+</jats:sup> inhibited <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. However, H<jats:sup>+</jats:sup> induced no further inhibition of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> in the presence of a saturating concentration of Zn<jats:sup>2+</jats:sup>. In addition, H<jats:sup>+</jats:sup> significantly affected the kinetics of glycinergic mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. It is proposed that H<jats:sup>+</jats:sup> and/or Zn<jats:sup>2+</jats:sup> compete with glycine binding and inhibit the amplitude of glycinergic mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. Moreover, binding of H<jats:sup>+</jats:sup> induces a global conformational change in GlyR, which closes the GlyR Cl<jats:sup>−</jats:sup> channel and results in the acceleration of the seeming desensitization of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> as well as speeding up the decay time constant of glycinergic mIPSCs. However, the deprotonation rate is faster than the unbinding rate of glycine from the GlyR, leading to reactivation of the undesensitized GlyR after washout of agonist and the appearance of a rebound <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. H<jats:sup>+</jats:sup> also modulated the glycine cotransmitter, GABA‐activated current (<jats:italic>I</jats:italic><jats:sub>GABA</jats:sub>). Taken together, the results support a ‘conformational coupling’ model for H<jats:sup>+</jats:sup> modulation of the GlyR and suggest that H<jats:sup>+</jats:sup> may act as a novel modulator for inhibitory neurotransmission in the mammalian spinal cord.</jats:p> |
| doi_str_mv | 10.1113/jphysiol.2003.047324 |
| facet_avail | Online, Free |
| finc_class_facet | Biologie |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMy9qcGh5c2lvbC4yMDAzLjA0NzMyNA |
| imprint | Wiley, 2003 |
| imprint_str_mv | Wiley, 2003 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
| issn | 0022-3751, 1469-7793 |
| issn_str_mv | 0022-3751, 1469-7793 |
| language | English |
| last_indexed | 2024-03-01T14:50:48.484Z |
| match_str | li2003mechanismsofhmodulationofglycinergicresponseinratsacraldorsalcommissuralneurons |
| mega_collection | Wiley (CrossRef) |
| physical | 73-87 |
| publishDate | 2003 |
| publishDateSort | 2003 |
| publisher | Wiley |
| record_format | ai |
| recordtype | ai |
| series | The Journal of Physiology |
| source_id | 49 |
| spelling | Li, Yan‐Fang Wu, Long‐Jun Li, Yong Xu, Lin Xu, Tian‐Le 0022-3751 1469-7793 Wiley Physiology http://dx.doi.org/10.1113/jphysiol.2003.047324 <jats:p>Many ionotropic receptors are modulated by extracellular H<jats:sup>+</jats:sup>. So far, few studies have directly addressed the role of such modulation at synapses. In the present study, we investigated the effects of changes in extracellular pH on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) as well as glycine‐evoked currents (<jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>) in mechanically dissociated spinal neurons with native synaptic boutons preserved. H<jats:sup>+</jats:sup> modulated both the mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> biphasically, although it activated an amiloride‐sensitive inward current by itself. Decreasing extracellular pH reversibly inhibited the amplitude of the mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>, while increasing external pH reversibly potentiated these parameters. Blockade of acid‐sensing ion channels (ASICs) with amiloride, the selective antagonist of ASICs, or decreasing intracellular pH did not alter the modulatory effect of H<jats:sup>+</jats:sup> on either mIPSCs or <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. H<jats:sup>+</jats:sup> shifted the EC<jats:sub>50</jats:sub> of the glycine concentration‐response curve from 49.3 ± 5.7 μ<jats:sc>m</jats:sc> at external pH 7.4 to 131.5 ± 8.1 μM at pH 5.5, without altering the Cl<jats:sup>−</jats:sup> selectivity of the glycine receptor (GlyR), the Hill coefficient and the maximal <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>, suggesting a competitive inhibition of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> by H<jats:sup>+</jats:sup>. Both Zn<jats:sup>2+</jats:sup> and H<jats:sup>+</jats:sup> inhibited <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. However, H<jats:sup>+</jats:sup> induced no further inhibition of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> in the presence of a saturating concentration of Zn<jats:sup>2+</jats:sup>. In addition, H<jats:sup>+</jats:sup> significantly affected the kinetics of glycinergic mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. It is proposed that H<jats:sup>+</jats:sup> and/or Zn<jats:sup>2+</jats:sup> compete with glycine binding and inhibit the amplitude of glycinergic mIPSCs and <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. Moreover, binding of H<jats:sup>+</jats:sup> induces a global conformational change in GlyR, which closes the GlyR Cl<jats:sup>−</jats:sup> channel and results in the acceleration of the seeming desensitization of <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub> as well as speeding up the decay time constant of glycinergic mIPSCs. However, the deprotonation rate is faster than the unbinding rate of glycine from the GlyR, leading to reactivation of the undesensitized GlyR after washout of agonist and the appearance of a rebound <jats:italic>I</jats:italic><jats:sub>Gly</jats:sub>. H<jats:sup>+</jats:sup> also modulated the glycine cotransmitter, GABA‐activated current (<jats:italic>I</jats:italic><jats:sub>GABA</jats:sub>). Taken together, the results support a ‘conformational coupling’ model for H<jats:sup>+</jats:sup> modulation of the GlyR and suggest that H<jats:sup>+</jats:sup> may act as a novel modulator for inhibitory neurotransmission in the mammalian spinal cord.</jats:p> Mechanisms of H<sup>+</sup> Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons The Journal of Physiology |
| spellingShingle | Li, Yan‐Fang, Wu, Long‐Jun, Li, Yong, Xu, Lin, Xu, Tian‐Le, The Journal of Physiology, Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons, Physiology |
| title | Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_full | Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_fullStr | Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_full_unstemmed | Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_short | Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| title_sort | mechanisms of h<sup>+</sup> modulation of glycinergic response in rat sacral dorsal commissural neurons |
| title_unstemmed | Mechanisms of H+ Modulation of Glycinergic Response in Rat Sacral Dorsal Commissural Neurons |
| topic | Physiology |
| url | http://dx.doi.org/10.1113/jphysiol.2003.047324 |