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Calcium influx‐independent depression of transmitter release by 5‐HT at lamprey spinal cord synapses
Author(s) -
Takahashi Michiko,
Freed Rachel,
Blackmer Trillium,
Alford Simon
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0323f.x
Subject(s) - neuroscience , excitatory postsynaptic potential , chemistry , glutamatergic , postsynaptic potential , lamprey , electrophysiology , neurotransmission , biophysics , glutamate receptor , inhibitory postsynaptic potential , biology , receptor , biochemistry , fishery
1 The mechanisms by which 5‐hydroxytryptamine (5‐HT) depresses transmitter release from lamprey reticulospinal axons were investigated. These axons make glutamatergic synapses onto spinal ventral horn neurons. 5‐HT reduces release at these synapses, yet the mechanisms remain unclear. 2 Excitatory postsynaptic currents (EPSCs) evoked by stimulation of reticulospinal axons were recorded in ventral horn neurons. 5‐HT depressed the EPSCs in a dose‐dependent manner with an apparent K m of 2.3 μ m . 3 To examine the presynaptic effect of 5‐HT, electrophysiological and optical recordings were made from presynaptic axons. Action potentials evoked Ca 2+ transients in the axons loaded with a Ca 2+ ‐sensitive dye. 5‐HT slightly reduced the Ca 2+ transient. 4 A third‐power relationship between Ca 2+ entry and transmitter release was determined. However, presynaptic Ca 2+ currents were unaffected by 5‐HT. 5 Further, in the presence of a K + channel blocker, 4‐aminopyridine (4‐AP), 5‐HT left unaltered the presynaptic Ca 2+ transient, ruling out the possibility of its direct action on presynaptic Ca 2+ current. 5‐HT activated a 4‐AP‐sensitive current with a reversal potential of ‐95 mV in these axons. 6 The basal Ca 2+ concentration did not affect 5‐HT‐mediated inhibition of release. Although 5‐HT caused a subtle reduction in resting axonal [Ca 2+ ] i , synaptic responses recorded during enhanced resting [Ca 2+ ] i , by giving stimulus trains, were equally depressed by 5‐HT. 7 5‐HT reduced the frequency of TTX‐insensitive spontaneous EPSCs at these synapses, but had no effect on their amplitude. We propose a mechanism of inhibition for transmitter release by 5‐HT that is independent of presynaptic Ca 2+ entry.