Substance P activates Cl and K+ conductances in guinea-pig tracheal smooth muscle cells

Substance P (SP) causes bronchoconstriction, but its effects on airway smooth muscle ion conductances are unknown. We investigated the effects of SP on single smooth muscle cells dissociated from guinea-pig trachealis. Under voltage clamp at -60 mV, SP evoked reversible contractions and inward current (ISP). ISP had a latency of approximately 1 s, reached a peak of 1039 +/- 147 pA (n = 19) about 2 s after onset of application, and declined to baseline levels over the next 5-10 s. At more positive holding potentials (-25 and 0 mV), the inward current was decreased in magnitude and preceded by outward current. With 140 mM K+ in the electrode and Cl- equilibrium potential (ECl) of about 0 mV, ISP was outwardly rectifying and reversed at -11 +/- 2 mV. When K+ currents were blocked using Cs+, the current-voltage relationship for ISP was linear and reversed at 3 +/- 1 mV. The reversal potential was dependent on the Cl- gradient across the membrane. These results suggest that SP caused a transient activation of Cl- and K+ conductances. Following the initial transient inward current, SP caused a prolonged suppression of spontaneously active K+ currents. The findings that SP evoked contractions during voltage clamp at potentials at which voltage-dependent Ca2+ channels are not active, and that current oscillations were also evoked by SP, suggest that SP is acting through release of Ca2+ from internal stores. Furthermore, SP occluded the inward current evoked by acetylcholine, suggesting that the peptidergic and cholinergic signalling pathways converge.(ABSTRACT TRUNCATED AT 250 WORDS)