Volume 17, Number 18,
Issue of September 15, 1997
pp. 6839-6849
Copyright ©1997 Society for Neuroscience
Serotonergic Inhibition of the T-Type and High Voltage-Activated
Ca2+ Currents in the Primary Sensory Neurons of
Xenopus Larvae
Received April 30, 1997; revised June 17, 1997; accepted June 26, 1997.
Qian-Quan Sun and
Nicholas Dale
School of Biological and Medical Sciences, St. Andrews University,
St. Andrews, Fife, KY16 9TS United Kingdom
The primary sensory Rohon-Beard (R-B) neurons of
Xenopus larvae are highly analogous to the C fibers of
the mammalian pain pathway. We explored the actions of 5-HT by studying
the modulation of Ca2+ currents. In ~80% of the
acutely isolated R-B neurons, 5-HT inhibited the high
voltage-activated (HVA) currents by 16% (n = 29)
and the T-type currents by 24% (n = 41). The
modulation of the T-type and the HVA currents was mimicked by selective
5-HT1A and 5-HT1D agonists: 8-OH-DPAT and
L-694,247. The effects of the agonists were blocked by their respective
5-HT1A or 5-HT1D antagonists: p-MPPI and GR127935, suggesting that both
5-HT1A and 5-HT1D receptors were involved.
Approximately 70% of the actions of 5-HT on HVA currents was occluded
by 
-conotoxin-GVIA (N-type channel blocker), whereas the rest of the
modulation (~30%) was occluded by <100 nM
-agatoxin-TK (P/Q-type channel blocker). This suggests that 5-HT
acts on N- and P/Q-type Ca2+ channels. Neither the
modulation of the T-type nor that of the HVA currents was accompanied
by changes in their voltage-dependent kinetics. Cell-attached
patch-clamp recordings suggest that the modulation of the T-type
channel occurs through a membrane-delimited second messenger. We have
studied the functional consequences of the modulation of T-type
Ca2+ channels and have found that these channels
play a role in spike initiation in R-B neurons. Modulation of T-type
channels by 5-HT therefore could modulate the sensitivity of this
sensory pathway by increasing the thresholds of R-B neurons. This is a
new and potentially important locus for modulation of sensory pathways in vertebrates.
Key words:
5-HT1A receptor;
5-HT1D receptor;
T-type Ca2+ currents;
-conotoxin-GVIA;
-agatoxin-TK;
spike initiation;
Xenopus;
Rohon-Beard
neurons
