Ch. Lin et al., Modulation of voltage-dependent calcium currents by serotonin in acutely isolated rat amygdala neurons, SYNAPSE, 41(4), 2001, pp. 351-359
The modulation of voltage-dependent calcium currents (I-Ca) by serotonin (5
-HT) was studied in rat acutely dissociated amygdala neurons using whole-ce
ll patch-clamp recording techniques. 5-HT inhibited I-Ca in a concentration
-dependent manner with a ED50 Of similar to1 muM and a maximal inhibition o
f similar to 50%. The inhibition was mimicked by the selective 5-HT1A agoni
st 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and was reduced by the 5-HT1
A antagonist NAN-190, indicating its mediation by 5-HT1A receptors. Pretrea
tment of neurons with the alkylating agent N-ethylmaleimide (NEM) or pertus
sis toxin (PTX) markedly reduced the action of 5-HT. The modulation was par
tially 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
muM) reduced the I-Ca by similar to 30% without reducing inhibition of curr
ent by 5-HT significantly, ruling out L-type channels as the target of modu
lation. 5-HT-mediated inhibition after exposure to omega -conotoxin-GVIA (o
mega -CgTX, 1 muM) or omega -agatoxin-IV (omega -AgTX, 200 nM), which block
ed 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 p
resence of w-CgTX and w-AgTX, 5-HT still caused a small but significant red
uction Of I-Ca, suggesting a possible involvement of R-type channels. Stimu
lation 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 pret
reatment. On the other hand, application of 8-OH-DPAT inhibited I-Ca and bl
ocked Iso- and Sp-cAMPS-induced enhancement. These results provide the firs
t evidence showing a dominant effect of 5-HT-mediated inhibition over Iso-m
ediated enhancement of I-Ca. (C) 2001 Wiley-Liss, Inc.