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Opposite effects of presynaptic 5‐HT 3 receptor activation on spontaneous and action potential‐evoked GABA release at hippocampal synapses
Author(s) -
Dorostkar Mario M.,
Boehm Stefan
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04218.x
Subject(s) - excitatory postsynaptic potential , inhibitory postsynaptic potential , postsynaptic potential , neuroscience , postsynaptic current , 5 ht receptor , chemistry , neurotransmission , hippocampal formation , glutamate receptor , serotonin , receptor , biology , biochemistry
5‐HT 3 (serotonin type 3) receptors are targets of antiemetics, antipsychotics, and antidepressants and are believed to play a role in cognition. Nevertheless, contrasting results have been obtained with respect to their functions in the CNS and in the control of transmitter release. We used rat hippocampal neurons in single‐neuron microcultures to identify the roles of presynaptic 5‐HT 3 receptors at central synapses. 5‐HT (10 μ m ) caused a transient > 10‐fold increase in the frequency of miniature inhibitory postsynaptic currents without affecting amplitudes or kinetics. This effect was abolished by tropisetron (30 n m ) and when Ca 2+ channels were blocked by 100 μ m Cd 2+ it was mimicked and occluded when neurons were depolarized by 20 m m , but not 10 m m , K + . Thus, activation of presynaptic 5‐HT 3 receptors increased spontaneous GABA release by causing depolarization and opening of voltage‐gated Ca 2+ channels. In microculture neurons, 5‐HT transiently reduced action potential‐evoked inhibitory autaptic currents by > 50%; this effect was blocked by tropisetron and mimicked by 20 m m , but not 10 m m , K + . Miniature excitatory postsynaptic currents were not altered by 5‐HT. Excitatory autaptic currents were tonically reduced, an effect attenuated by 5‐HT 1A antagonists. Thus, presynaptic 5‐HT 3 receptors control GABA, but not glutamate, release and mediate opposite effects on spontaneous and action potential‐dependent release.