ACTIONS OF SUBSTANCE-P ON MEMBRANE-POTENTIAL AND IONIC CURRENTS IN GUINEA-PIG STELLATE GANGLION NEURONS

Neuropeptides are known to modulate the excitability of mammalian symp athetic neurons by their actions on various types of K+ and Ca2+ chann els. We used whole cell patch-clamp recording methods to study the act ions of substance P (SP) on dissociated adult guinea pig stellate gang lion (SG) neurons. Under current-clamp conditions, SG neurons exhibite d overshooting action potentials followed by afterhyperpolarizations ( AHP). The K+ channel blocker tetraethylammonium (1 mM), the Ca2+ chann el blocker Cd2+ (0.1-0.2 mM), and SP (500 nM) depolarized SG neurons, decreased the AHP amplitude, and increased the action potential durati on. In the presence of Cd2+, the effect of SP on membrane potential an d 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 (I-K) consisting of Ca2+-s ensitive [I-K(Ca)] and Ca2+-insensitive components. SP (500 nM) inhibi ted I-K. Pretreatment with Cd2+ (20-200 mu M) or the high-voltage-acti vated Ca2+ channel blocker omega-conotoxin (10 mu M) blocked SP's inhi bitory effects on I-K. This suggests that SP reduces I-K primarily thr ough the inhibition of I-K(Ca) and that this may occur, in part, via a reduction of Ca2+ influx through voltage-dependent Ca2+ channels. SP' s actions on I-K were mediated by a pertussis toxin-insensitive G prot ein(s) coupled to NK1 tachykinin receptors. Furthermore, we have confi rmed that 500 nM SP reduced an inward Cd2+- and omega-conotoxin-sensit ive Ba2+ current in SG neurons. Thus the actions of SP on I-K(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 excitab ility in SG neurons via inhibitory actions on K+ and Ca2+ currents.