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

@article{citeulike:2279160, abstract = {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 ED50 of approximately 1 microM and a maximal inhibition of approximately 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 microM) reduced the I(Ca) by approximately 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 omega-conotoxin-GVIA (omega-CgTX, 1 microM) or omega-agatoxin-IV (omega-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 omega-CgTX and omega-AgTX, 5-HT still caused a small but significant reduction of I(Ca), suggesting a possible involvement of R-type channels. Stimulation of beta-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).}, address = {Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan 701.}, author = {Lin, C. H. and Huang, Y. C. and Tsai, J. J. and Gean, P. W. }, citeulike-article-id = {2279160}, issn = {0887-4476}, journal = {Synapse}, keywords = {5-ht, amygdala, vdcc}, month = {September}, number = {4}, pages = {351--359}, posted-at = {2008-01-23 06:53:07}, priority = {0}, title = {Modulation of voltage-dependent calcium currents by serotonin in acutely isolated rat amygdala neurons.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11494406}, volume = {41}, year = {2001} }

TY - JOUR ID - citeulike:2279160 L3 - citeulike-article-id:2279160 TI - Modulation of voltage-dependent calcium currents by serotonin in acutely isolated rat amygdala neurons. JF - Synapse VL - 41 IS - 4 SP - 351 EP - 359 AD - Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan 701. SN - 0887-4476 N2 - 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 ED50 of approximately 1 microM and a maximal inhibition of approximately 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 microM) reduced the I(Ca) by approximately 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 omega-conotoxin-GVIA (omega-CgTX, 1 microM) or omega-agatoxin-IV (omega-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 omega-CgTX and omega-AgTX, 5-HT still caused a small but significant reduction of I(Ca), suggesting a possible involvement of R-type channels. Stimulation of beta-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). KW - 5-ht KW - amygdala KW - vdcc AU - Lin, CH AU - Huang, YC AU - Tsai, JJ AU - Gean, PW PY - 2001/09/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/11494406 ER -