We investigated the effect of chronically blocking NMDA receptor stimulation to examine changes in GABAA receptor expression and pharmacology in cerebellar granule cells at different stages of maturation. We have previously shown that NMDA-selective glutamate receptor stimulation alters GABAA receptor pharmacology in cerebellar granule neurons in vitro by altering the levels of selective subunits. When NMDA receptor stimulation is blocked with MK-801 during the first week in vitro, a decrease in the α1, γ2S, and γ2L receptor subunit mRNAs occurred. When present only during the second week, changes were limited to the α1 and γ2L mRNAs. Finally, if MK-801 was present during the first week and removed during the second week, these changes reversed. Whole-cell voltage-clamp recordings showed that treatment with MK-801 during either the first or second week increased the EC50 of the receptors for GABA and attenuated the potentiation mediated by flunitrazepam. Last, these properties were reversed if MK-801 was removed after the first week in vitro. Our results suggest that MK-801 reversibly inhibits GABAA receptor maturation by modulating receptor subunit expression and that the altered pharmacological responses appear to be dominated by changes in the levels of allosteric modulation mediated by the γ2 receptor subunit.

Chronic dizolcipine (MK 801) reversibly delays GabaA receptor maturation in cerebellar granule neurons in vitro / Wang, X. H.; Zhu, W. J.; Corsi, L.; Ikonomovic, S.; Paljung, W. R.; Vicini, S.; Grayson, D. R.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - STAMPA. - 71:(1998), pp. 693-704.

Chronic dizolcipine (MK 801) reversibly delays GabaA receptor maturation in cerebellar granule neurons in vitro.

CORSI, L.;
1998

Abstract

We investigated the effect of chronically blocking NMDA receptor stimulation to examine changes in GABAA receptor expression and pharmacology in cerebellar granule cells at different stages of maturation. We have previously shown that NMDA-selective glutamate receptor stimulation alters GABAA receptor pharmacology in cerebellar granule neurons in vitro by altering the levels of selective subunits. When NMDA receptor stimulation is blocked with MK-801 during the first week in vitro, a decrease in the α1, γ2S, and γ2L receptor subunit mRNAs occurred. When present only during the second week, changes were limited to the α1 and γ2L mRNAs. Finally, if MK-801 was present during the first week and removed during the second week, these changes reversed. Whole-cell voltage-clamp recordings showed that treatment with MK-801 during either the first or second week increased the EC50 of the receptors for GABA and attenuated the potentiation mediated by flunitrazepam. Last, these properties were reversed if MK-801 was removed after the first week in vitro. Our results suggest that MK-801 reversibly inhibits GABAA receptor maturation by modulating receptor subunit expression and that the altered pharmacological responses appear to be dominated by changes in the levels of allosteric modulation mediated by the γ2 receptor subunit.
71
693
704
Chronic dizolcipine (MK 801) reversibly delays GabaA receptor maturation in cerebellar granule neurons in vitro / Wang, X. H.; Zhu, W. J.; Corsi, L.; Ikonomovic, S.; Paljung, W. R.; Vicini, S.; Grayson, D. R.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - STAMPA. - 71:(1998), pp. 693-704.
Wang, X. H.; Zhu, W. J.; Corsi, L.; Ikonomovic, S.; Paljung, W. R.; Vicini, S.; Grayson, D. R.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/609222
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 17
social impact