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Departments of 1 Pharmacology, 2 Physiology and Biophysics, and 3 Anatomy and Neurobiology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7
Neuropeptides are known to modulate the excitability of
mammalian sympathetic neurons by their actions on various types of K+ and
Ca2+ channels. We used whole cell
patch-clamp recording methods to study the actions of substance P (SP)
on dissociated adult guinea pig stellate ganglion (SG) neurons. Under
current-clamp conditions, SG neurons exhibited overshooting action
potentials followed by afterhyperpolarizations (AHP). The
K+ channel blocker
tetraethylammonium (1 mM), the
Ca2+ channel blocker
Cd2+ (0.1-0.2 mM), and SP
(500 nM) depolarized SG neurons, decreased the AHP amplitude, and
increased the action potential duration. In the presence of
Cd2+, the effect of SP on membrane
potential and AHP was reduced. Under voltage-clamp conditions, several
different K+ currents were
observed, including a transient outward
K+ conductance and a delayed
rectifier outward K+ current
(IK) consisting
of Ca2+-sensitive
[IK(Ca)]
and Ca2+-insensitive components.
SP (500 nM) inhibited
IK. Pretreatment with Cd2+ (20-200
µM) or the high-voltage-activated
Ca2+ channel blocker 
-conotoxin
(10 µM) blocked SP's inhibitory effects on
IK. This suggests
that SP reduces
IK primarily
through the inhibition of
IK(Ca) and that
this may occur, in part, via a reduction of
Ca2+ influx through
voltage-dependent Ca2+ channels.
SP's actions on
IK were mediated
by a pertussis toxin-insensitive G protein(s) coupled to
NK1 tachykinin receptors.
Furthermore, we have confirmed that 500 nM SP reduced an inward
Cd2+- and -conotoxin-sensitive
Ba2+ current in SG neurons. Thus
the actions of SP on
IK(Ca) may be due
in part to a reduction in Ca2+
influx occurring via N-type Ca2+
channels. This study presents the first description of ionic currents
in mammalian SG neurons and demonstrates that SP may modulate
excitability in SG neurons via inhibitory actions on K+ and
Ca2+ currents.
G protein; patch clamp; tachykinin; -conotoxin
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