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Next Article 
Volume 17, Number 19,
Issue of October 1, 1997
pp. 7181-7189
Copyright ©1997 Society for Neuroscience
5HT4 Receptors Couple Positively to
Tetrodotoxin-Insensitive Sodium Channels in a Subpopulation of
Capsaicin-Sensitive Rat Sensory Neurons
Received April 8, 1997; revised July 3, 1997; accepted July 11, 1997.
Carla G. Cardenas1,
Lucinda P. Del Mar1,
Brian
Y. Cooper2, and
Reese S. Scroggs1
1 University of Tennessee, College of Medicine,
Department of Anatomy and Neurobiology, Memphis, Tennessee 38163, and
2 University of Florida, College of Dentistry, Department
of Oral and Maxillofacial Surgery, Gainesville, Florida 32610
The distribution of tetrodotoxin (TTX)-sensitive and -insensitive
Na+ currents and their modulation by serotonin (5HT)
and prostaglandin E2 (PGE2) was studied
in four different types of dorsal root ganglion (DRG) cell bodies
(types 1, 2, 3, and 4), which were previously identified on the basis
of differences in membrane properties (). Types 1 and 2 DRG cells expressed TTX-insensitive Na+
currents, whereas types 3 and 4 DRG cells exclusively expressed TTX-sensitive Na+ currents.
Application of 5HT (1-10 µM) increased TTX-insensitive
Na+ currents in type 2 DRG cells but did not affect
Na+ currents in type 1, 3, or 4 DRG cells. The 5HT
receptor involved resembled the 5HT4 subtype. It was
activated by 5-methoxy-N,N-dimethyltryptamine (10 µM) but not by 5-carboxyamidotryptamine (1 µM), (+)-8-hydroxydipropylaminotetralin (10 µM), or 2-methyl-5HT (10 µM), and was
blocked by ICS 205-930 with an EC50 of ~2
µM but not by ketanserin (1 µM).
PGE2 (4 or 10 µM) also increased
Na+ currents in varying portions of cells in all
four groups.
The effect of 5HT and PGE2 on Na+
currents was delayed for 20-30 sec after exposure to 5HT, suggesting
the involvement of a cytosolic diffusible component in the signaling
pathway. The agonist-mediated increase in Na+
current, however, was not mimicked by 8-chlorophenylthio-cAMP (200 µM), suggesting the possibility that cAMP was not
involved.
The data suggest that the 5HT- and PGE2-mediated increase
in Na+ current may be involved in hyperesthesia in
different but overlapping subpopulations of nociceptors.
Key words:
serotonin;
PGE2;
capsaicin;
nociceptor;
tetrodotoxin;
cAMP;
dorsal root ganglion;
5HT4
receptor
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