SUBSTANCE-P ACTIVATES CL- AND K-PIG TRACHEAL SMOOTH-MUSCLE CELLS( CONDUCTANCES IN GUINEA)

Substance P (SP) causes bronchoconstriction, but its effects on airway smooth muscle ion conductances are unknown. We investigated the effec ts of SP on single smooth muscle cells dissociated from guinea-pig tra chealis. Under voltage clamp at -60 mV, SP evoked reversible contracti ons and inward current (I-SP).I-SP had a latency of approximately 1 s, reached a peak of 1039 +/- 147 pA (n = 19) about 2 s after onset of a pplication, and declined to baseline levels over the next 5-10 s. At m ore 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 (E(Cl)) of about 0 mV , I-SP was outwardly rectifying and reversed at -11 +/- 2 mV. When Kcurrents were blocked using Cs+, the current-voltage relationship for I-SP was linear and reversed at 3 +/- 1 mV. The reversal potential was dependent on the Cl- gradient across the membrane. These results sugg est 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 voltag e-dependent Ca2+ channels are not active, and that current oscillation s were also evoked by SP, suggest that SP is acting through release of Ca2+ from internal stores. Furthermore, SP occluded the inward curren t evoked by acetylcholine, suggesting that the peptidergic and choline rgic signalling pathways converge. We conclude that SP releases Ca2+ f rom internal stores in guinea-pig airway smooth muscle cells, leading to activation of Cl- and K+ conductances, depolarization, and contract ion.