Janssen L J, Sims S M
Department of Physiology, University of Western Ontario, London, Canada.
Can J Physiol Pharmacol. 1994 Jun;72(6):705-10. doi: 10.1139/y94-100.
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)
P物质（SP）可引起支气管收缩，但其对气道平滑肌离子电导的影响尚不清楚。我们研究了SP对从豚鼠气管分离的单个平滑肌细胞的影响。在-60 mV电压钳制下，SP诱发可逆性收缩和内向电流（ISP）。ISP的潜伏期约为1秒，在施加后约2秒达到峰值1039±147 pA（n = 19），并在接下来的5 - 10秒内降至基线水平。在更正的钳制电位（-25和0 mV）下，内向电流幅度减小并先出现外向电流。当电极中含有140 mM K⁺且Cl⁻平衡电位（ECl）约为0 mV时，ISP呈外向整流，在-11±2 mV时反转。当使用Cs⁺阻断K⁺电流时，ISP的电流 - 电压关系呈线性，在3±1 mV时反转。反转电位取决于跨膜Cl⁻梯度。这些结果表明，SP引起Cl⁻和K⁺电导的瞬时激活。在最初的瞬时内向电流之后，SP导致自发活动的K⁺电流长期受到抑制。SP在电压依赖性Ca²⁺通道不活跃的电位下电压钳制期间诱发收缩，以及SP也诱发电流振荡的发现表明，SP通过从内部储存释放Ca²⁺起作用。此外，SP阻断了乙酰胆碱诱发的内向电流，表明肽能和胆碱能信号通路汇聚。（摘要截断于250字）
