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Serotonin induces depolarization in lateral amygdala neurons by activation of TRPC-like current and inhibition of GIRK current depending on 5-HT(2C) receptor.

Abstract：

:Regional differences are known in the serotonin-induced modulation of neuronal activity within the amygdala. This in vitro study in rats focuses on analyzing the ionic mechanism underlying serotonin-induced depolarization in the lateral amygdala. Serotonin depolarized membrane potential by 5 mV, which is underlain by a serotonin-induced inward current at rest with a characteristic reversal potential of -105 mV. From pharmacological experiments, the 5-HT2C subtype was singled out as the receptor subtype involved. Under blockade of K(+) channels by Ba(2+), 5-HT induced an inward current with no reversal at the range between -50 and -130 mV, which was identified as a TRPC-like current. This current was blocked by the specific phosphatidylinositol 3-kinse (PI3-kinase) inhibitor LY294002, pointing to its dependence on PI3-kinase. The Ba(2+)-sensitive component, obtained by subtraction, showed a strong outward rectification and the reversal potential of K(+), indicating that this component results from a serotonin-induced inhibition of G-protein coupled inwardly rectifying K(+) channel (GIRK) current. By wortmannin, an inhibitor of both PI3-kinase and PI4-kinase, a serotonin-induced phosphatidylinositol 4,5-bisphosphate (PIP2) depletion was revealed to underlie GIRK inhibition. Thus, the serotonin-induced current turned out to be caused by a combined occurrence of GIRK inhibition and PI3-kinase-dependent TRPC-like current. With serotonergic modulation, all these mechanisms should be recruited in lateral amygdala principal neurons and likely contribute to generation of region-specific neuronal activity patterns within the amygdala, which may at least partly implement its required role in fear and anxiety.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Yamamoto R,Hatano N,Sugai T,Kato N

doi

10.1016/j.neuropharm.2014.03.007

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

49-58

eissn

0028-3908

issn

1873-7064

pii

S0028-3908(14)00092-6

journal_volume

pub_type

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Serotonin induces depolarization in lateral amygdala neurons by activation of TRPC-like current and inhibition of GIRK current depending on 5-HT(2C) receptor.