The calcineurin inhibitor cyclosporin A-cyclophilin A complex reduces desensitization of GABA(A)-mediated responses in acutely dissociated rat hippocampal neurons

M. Martina, J. W. Mozrzymas, H. W G M Boddeke, E. Cherubini*

*Corresponding author for this work

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The effects of the selective inhibitor of calcineurin, cyclosporin A-cyclophilin A (CC) complex on the desensitization kinetics of GABA(A) receptors was studied in acutely dissociated hippocampal neurons, using the patch clamp technique in the whole cell configuration. In control conditions, the decay of GABA-evoked current could be fitted by a biexponential function having time constants of 0.65 ± 0.24 s and 3.75 ± 2 s. The plateau to peak ratio was 0.087 ± 0.034. Recovery from desensitization was obtained in more than 2 min. In cells dialyzed with the CC complex, the decay of the currents could be fitted with the sum of two exponentials having time constants similar to controls (0.81 ± 0.47 s and 3.62 ± 2.1 s), but the percentage of the fast component was smaller. The plateau to peak ratio was significantly larger than control (0.185 ± 0.07). With CC complex, recovery from desensitization was completed in almost 30 s. The cyclosporin A derivative PSC 833, which does not inhibit calcineurin, did not affect desensitization kinetics. These results suggest that phosphatase 2B regulates desensitization of GABA(A) receptors.

Original languageEnglish (US)
Pages (from-to)95-98
Number of pages4
JournalNeuroscience Letters
Volume215
Issue number2
DOIs
StatePublished - Sep 6 1996

Fingerprint

Cyclophilin A
gamma-Aminobutyric Acid
Cyclosporine
GABA-A Receptors
Neurons
Calcineurin
Patch-Clamp Techniques
Phosphoric Monoester Hydrolases
Calcineurin Inhibitors

Keywords

  • A-cyclophilin A complex
  • Cyclosporin
  • Desensitization
  • GABA(A)
  • Hippocampus
  • Patch clamp
  • Recovery from desensitization

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "The calcineurin inhibitor cyclosporin A-cyclophilin A complex reduces desensitization of GABA(A)-mediated responses in acutely dissociated rat hippocampal neurons",
abstract = "The effects of the selective inhibitor of calcineurin, cyclosporin A-cyclophilin A (CC) complex on the desensitization kinetics of GABA(A) receptors was studied in acutely dissociated hippocampal neurons, using the patch clamp technique in the whole cell configuration. In control conditions, the decay of GABA-evoked current could be fitted by a biexponential function having time constants of 0.65 ± 0.24 s and 3.75 ± 2 s. The plateau to peak ratio was 0.087 ± 0.034. Recovery from desensitization was obtained in more than 2 min. In cells dialyzed with the CC complex, the decay of the currents could be fitted with the sum of two exponentials having time constants similar to controls (0.81 ± 0.47 s and 3.62 ± 2.1 s), but the percentage of the fast component was smaller. The plateau to peak ratio was significantly larger than control (0.185 ± 0.07). With CC complex, recovery from desensitization was completed in almost 30 s. The cyclosporin A derivative PSC 833, which does not inhibit calcineurin, did not affect desensitization kinetics. These results suggest that phosphatase 2B regulates desensitization of GABA(A) receptors.",
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The calcineurin inhibitor cyclosporin A-cyclophilin A complex reduces desensitization of GABA(A)-mediated responses in acutely dissociated rat hippocampal neurons. / Martina, M.; Mozrzymas, J. W.; Boddeke, H. W G M; Cherubini, E.

In: Neuroscience Letters, Vol. 215, No. 2, 06.09.1996, p. 95-98.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The calcineurin inhibitor cyclosporin A-cyclophilin A complex reduces desensitization of GABA(A)-mediated responses in acutely dissociated rat hippocampal neurons

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AU - Boddeke, H. W G M

AU - Cherubini, E.

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AB - The effects of the selective inhibitor of calcineurin, cyclosporin A-cyclophilin A (CC) complex on the desensitization kinetics of GABA(A) receptors was studied in acutely dissociated hippocampal neurons, using the patch clamp technique in the whole cell configuration. In control conditions, the decay of GABA-evoked current could be fitted by a biexponential function having time constants of 0.65 ± 0.24 s and 3.75 ± 2 s. The plateau to peak ratio was 0.087 ± 0.034. Recovery from desensitization was obtained in more than 2 min. In cells dialyzed with the CC complex, the decay of the currents could be fitted with the sum of two exponentials having time constants similar to controls (0.81 ± 0.47 s and 3.62 ± 2.1 s), but the percentage of the fast component was smaller. The plateau to peak ratio was significantly larger than control (0.185 ± 0.07). With CC complex, recovery from desensitization was completed in almost 30 s. The cyclosporin A derivative PSC 833, which does not inhibit calcineurin, did not affect desensitization kinetics. These results suggest that phosphatase 2B regulates desensitization of GABA(A) receptors.

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