Modulation of voltage-dependent calcium currents by serotonin in acutely isolated rat amygdala neurons

Chih Hung Lin, Ya Chun Huang, Jing Jane Tsai, Po-Wu Gean

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The modulation of voltage-dependent calcium currents (ICa) by serotonin (5-HT) was studied in rat acutely dissociated amygdala neurons using whole-cell patch-clamp recording techniques. 5-HT inhibited ICa in a concentration-dependent manner with a ED50 of ∼1 μM and a maximal inhibition of ∼50%. The inhibition was mimicked by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and was reduced by the 5-HT1A antagonist NAN-190, indicating its mediation by 5-HT1A receptors. Pretreatment of neurons with the alkylating agent N-ethylmaleimide (NEM) or pertussis toxin (PTX) markedly reduced the action of 5-HT. The modulation was partially reversed by strong depolarization and was not seen in cell-attached patches when the agonist was applied outside the recorded patch, suggesting a membrane-delimited, G-protein-mediated signaling pathway. Nimodipine (1 μM) reduced the ICa by ∼30% without reducing inhibition of current by 5-HT significantly, ruling out L-type channels as the target of modulation. 5-HT-mediated inhibition after exposure to ω-conotoxin-GVIA (ω-CgTX, 1 μM) or ω-agatoxin-IV (ω-AgTX, 200 nM), which blocked 26% and 21% of the total ICa, respectively, was significantly decreased, suggesting involvement of the N- and P/Q-type channels. In the combined presence of ω-CgTX and ω-AgTX, 5-HT still caused a small but significant reduction of ICa, suggesting a possible involvement of R-type channels. Stimulation of β-adrenergic receptor with isoproterenol (Iso) or activation of adenylyl cyclase with forskolin resulted in an enhancement of ICa. 5-HT caused the same degree of inhibition with or without Iso or forskolin pretreatment. On the other hand, application of 8-OH-DPAT inhibited ICa and blocked Iso- and Sp-cAMPS-induced enhancement. These results provide the first evidence showing a dominant effect of 5-HT-mediated inhibition over Iso-mediated enhancement of ICa.

Original languageEnglish
Pages (from-to)351-359
Number of pages9
JournalSynapse
Volume41
Issue number4
DOIs
Publication statusPublished - 2001 Sep 15

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Amygdala
Serotonin
Calcium
Neurons
Isoproterenol
8-Hydroxy-2-(di-n-propylamino)tetralin
Colforsin
Agatoxins
Conotoxins
Serotonin 5-HT1 Receptor Antagonists
Serotonin 5-HT1 Receptor Agonists
Nimodipine
Receptor, Serotonin, 5-HT1A
Ethylmaleimide
Alkylating Agents
Pertussis Toxin
Patch-Clamp Techniques
GTP-Binding Proteins
Adenylyl Cyclases
Adrenergic Receptors

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Lin, Chih Hung ; Huang, Ya Chun ; Tsai, Jing Jane ; Gean, Po-Wu. / Modulation of voltage-dependent calcium currents by serotonin in acutely isolated rat amygdala neurons. In: Synapse. 2001 ; Vol. 41, No. 4. pp. 351-359.
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abstract = "The modulation of voltage-dependent calcium currents (ICa) by serotonin (5-HT) was studied in rat acutely dissociated amygdala neurons using whole-cell patch-clamp recording techniques. 5-HT inhibited ICa in a concentration-dependent manner with a ED50 of ∼1 μM and a maximal inhibition of ∼50{\%}. The inhibition was mimicked by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and was reduced by the 5-HT1A antagonist NAN-190, indicating its mediation by 5-HT1A receptors. Pretreatment of neurons with the alkylating agent N-ethylmaleimide (NEM) or pertussis toxin (PTX) markedly reduced the action of 5-HT. The modulation was partially reversed by strong depolarization and was not seen in cell-attached patches when the agonist was applied outside the recorded patch, suggesting a membrane-delimited, G-protein-mediated signaling pathway. Nimodipine (1 μM) reduced the ICa by ∼30{\%} without reducing inhibition of current by 5-HT significantly, ruling out L-type channels as the target of modulation. 5-HT-mediated inhibition after exposure to ω-conotoxin-GVIA (ω-CgTX, 1 μM) or ω-agatoxin-IV (ω-AgTX, 200 nM), which blocked 26{\%} and 21{\%} of the total ICa, respectively, was significantly decreased, suggesting involvement of the N- and P/Q-type channels. In the combined presence of ω-CgTX and ω-AgTX, 5-HT still caused a small but significant reduction of ICa, suggesting a possible involvement of R-type channels. Stimulation of β-adrenergic receptor with isoproterenol (Iso) or activation of adenylyl cyclase with forskolin resulted in an enhancement of ICa. 5-HT caused the same degree of inhibition with or without Iso or forskolin pretreatment. On the other hand, application of 8-OH-DPAT inhibited ICa and blocked Iso- and Sp-cAMPS-induced enhancement. These results provide the first evidence showing a dominant effect of 5-HT-mediated inhibition over Iso-mediated enhancement of ICa.",
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Modulation of voltage-dependent calcium currents by serotonin in acutely isolated rat amygdala neurons. / Lin, Chih Hung; Huang, Ya Chun; Tsai, Jing Jane; Gean, Po-Wu.

In: Synapse, Vol. 41, No. 4, 15.09.2001, p. 351-359.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Modulation of voltage-dependent calcium currents by serotonin in acutely isolated rat amygdala neurons

AU - Lin, Chih Hung

AU - Huang, Ya Chun

AU - Tsai, Jing Jane

AU - Gean, Po-Wu

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N2 - The modulation of voltage-dependent calcium currents (ICa) by serotonin (5-HT) was studied in rat acutely dissociated amygdala neurons using whole-cell patch-clamp recording techniques. 5-HT inhibited ICa in a concentration-dependent manner with a ED50 of ∼1 μM and a maximal inhibition of ∼50%. The inhibition was mimicked by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and was reduced by the 5-HT1A antagonist NAN-190, indicating its mediation by 5-HT1A receptors. Pretreatment of neurons with the alkylating agent N-ethylmaleimide (NEM) or pertussis toxin (PTX) markedly reduced the action of 5-HT. The modulation was partially reversed by strong depolarization and was not seen in cell-attached patches when the agonist was applied outside the recorded patch, suggesting a membrane-delimited, G-protein-mediated signaling pathway. Nimodipine (1 μM) reduced the ICa by ∼30% without reducing inhibition of current by 5-HT significantly, ruling out L-type channels as the target of modulation. 5-HT-mediated inhibition after exposure to ω-conotoxin-GVIA (ω-CgTX, 1 μM) or ω-agatoxin-IV (ω-AgTX, 200 nM), which blocked 26% and 21% of the total ICa, respectively, was significantly decreased, suggesting involvement of the N- and P/Q-type channels. In the combined presence of ω-CgTX and ω-AgTX, 5-HT still caused a small but significant reduction of ICa, suggesting a possible involvement of R-type channels. Stimulation of β-adrenergic receptor with isoproterenol (Iso) or activation of adenylyl cyclase with forskolin resulted in an enhancement of ICa. 5-HT caused the same degree of inhibition with or without Iso or forskolin pretreatment. On the other hand, application of 8-OH-DPAT inhibited ICa and blocked Iso- and Sp-cAMPS-induced enhancement. These results provide the first evidence showing a dominant effect of 5-HT-mediated inhibition over Iso-mediated enhancement of ICa.

AB - The modulation of voltage-dependent calcium currents (ICa) by serotonin (5-HT) was studied in rat acutely dissociated amygdala neurons using whole-cell patch-clamp recording techniques. 5-HT inhibited ICa in a concentration-dependent manner with a ED50 of ∼1 μM and a maximal inhibition of ∼50%. The inhibition was mimicked by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and was reduced by the 5-HT1A antagonist NAN-190, indicating its mediation by 5-HT1A receptors. Pretreatment of neurons with the alkylating agent N-ethylmaleimide (NEM) or pertussis toxin (PTX) markedly reduced the action of 5-HT. The modulation was partially reversed by strong depolarization and was not seen in cell-attached patches when the agonist was applied outside the recorded patch, suggesting a membrane-delimited, G-protein-mediated signaling pathway. Nimodipine (1 μM) reduced the ICa by ∼30% without reducing inhibition of current by 5-HT significantly, ruling out L-type channels as the target of modulation. 5-HT-mediated inhibition after exposure to ω-conotoxin-GVIA (ω-CgTX, 1 μM) or ω-agatoxin-IV (ω-AgTX, 200 nM), which blocked 26% and 21% of the total ICa, respectively, was significantly decreased, suggesting involvement of the N- and P/Q-type channels. In the combined presence of ω-CgTX and ω-AgTX, 5-HT still caused a small but significant reduction of ICa, suggesting a possible involvement of R-type channels. Stimulation of β-adrenergic receptor with isoproterenol (Iso) or activation of adenylyl cyclase with forskolin resulted in an enhancement of ICa. 5-HT caused the same degree of inhibition with or without Iso or forskolin pretreatment. On the other hand, application of 8-OH-DPAT inhibited ICa and blocked Iso- and Sp-cAMPS-induced enhancement. These results provide the first evidence showing a dominant effect of 5-HT-mediated inhibition over Iso-mediated enhancement of ICa.

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