M. Takahashi et al., Calcium influx-independent depression of transmitter release by 5-HT at lamprey spinal cord synapses, J PHYSL LON, 532(2), 2001, pp. 323-336
1. The mechanisms by which 5-hydroxytryptamine (5-HT) depresses transmitter
release from lamprey reticulospinal axons were investigated. These axone m
ake glutamatergic synapses onto spinal ventral horn neurons. 5-HT reduces r
elease at these synapses, yet the mechanisms remain unclear.
2. Excitatory postsynaptic currents (EPSCs) evoked by stimulation of reticu
lospinal axons were recorded in ventral horn neurons. 5-HT depressed the EP
XCs in a dose-dependent manner with an apparent K-m of 2.3 muM.
3. To examine the presynaptic effect of 5-HT, electrophysiological and opti
cal recordings were made from presynaptic axons. Action potentials evoked C
a2+ transients in the axons loaded with a Ca2+-sensitive dye. 5-HT slightly
reduced the Ca2+ transient.
4. A third-power relationship between Ca2+ entry and transmitter release wa
s determined. However, presynaptic Ca2+ 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 Ca2+ transient, ruling out the possib
ility of its direct action on presynaptic Ca2+ current. 5-HT activated a 4-
AP-sensitive current with a reversal potential of -95 mV in these axons.
6. The basal Ca2+ concentration did not affect 5-HT-mediated inhibition of
release. Although 5-HT caused a subtle reduction in resting axonal [Ca2+](i
), synaptic responses recorded during enhanced resting [Ca2+](i), by giving
stimulus trains, were equally depressed by 5-HT.
7. 5-HT reduced the frequency of TTX-insensitive spontaneous EPXCs 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 presynapt
ic Ca2+ entry.