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 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 (I(K)) consisting of Ca²⁺-sensitive [I(K(Ca))] and Ca²⁺- insensitive components. SP (500 nM) inhibited I(K). Pretreatment with Cd²⁺ (20-200 μM) or the high-voltage-activated Ca²⁺ channel blocker ω- conotoxin (10 μM) blocked SP's inhibitory effects on I(K). This suggests that SP reduces I(K) primarily through 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 protein(s) coupled to NK₁ tachykinin receptors. Furthermore, we have confirmed that 500 nM SP reduced an inward Cd²⁺- and ω-conotoxin-sensitive 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 excitability in SG neurons via inhibitory actions on K⁺ and Ca²⁺ currents.