Premium
Modulation of voltage‐dependent calcium currents by serotonin in acutely isolated rat amygdala neurons
Author(s) -
Lin ChihHung,
Huang YaChun,
Tsai JingJane,
Gean PoWu
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.1092
Subject(s) - chemistry , agonist , adenylyl cyclase , pertussis toxin , forskolin , serotonin , patch clamp , endocrinology , medicine , voltage dependent calcium channel , 5 ht receptor , receptor , g protein , pharmacology , biophysics , calcium , biology , biochemistry , organic chemistry
The modulation of voltage‐dependent calcium currents (I Ca ) by serotonin (5‐HT) was studied in rat acutely dissociated amygdala neurons using whole‐cell patch‐clamp recording techniques. 5‐HT inhibited I Ca in a concentration‐dependent manner with a ED 50 of ∼1 μM and a maximal inhibition of ∼50%. The inhibition was mimicked by the selective 5‐HT 1A agonist 8‐hydroxy‐dipropylaminotetralin (8‐OH‐DPAT) and was reduced by the 5‐HT 1A antagonist NAN‐190, indicating its mediation by 5‐HT 1A 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 I Ca 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 I Ca , 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 I Ca , 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 I Ca . 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 I Ca 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 I Ca . Synapse 41:351–359, 2001. © 2001 Wiley‐Liss, Inc.