Neurokinin-1 receptor antagonist decreases [Ca2+]i in airway smooth muscle cells by reducing the reverse-mode Na+/Ca2+ exchanger current

Abstract Airway smooth muscle (ASM) is involved in asthma airway inflammation. The aim of this study was to evaluate the effect of substance P and neurokinin-1 receptor (NK-1R) antagonist on intracellular calcium concentration ([Ca 2+ ]i) in airway smooth muscle cells (ASMCs), ASMC contraction, and the effect on reverse-mode Na + –Ca 2+ exchanger (NCX) currents in ASMCs. In our study, primary rat ASMCs were cultured. ASMCs were identified by immunofluorescence. [Ca 2+ ]i variations were measured by fluorescence microscopy. Cell shortening (%) and relaxation (%) were analyzed with phase-contrast microscopy. Patch clamp techniques were used to assess NCX currents in ASMCs. We found that substance P increased, and NK-1R antagonist decreased [Ca 2+ ]i in ASMCs. Substance P induced ASMCs contraction, and NK-1R antagonist can make ASMC relax. Patch clamp techniques were implemented to analyze NCX currents in ASMCs. Substance P increased reverse-mode NCX currents in ASMCs but the current density was lower than the one treated with acetylcholine (Ach). NK-1R antagonist reduced reverse-mode NCX current activity in ASMCs, and the current density was similar to the one treated with the reversed NCX inhibitor. So, we concluded that substance P increased [Ca 2+ ]i in ASMCs by promoting the reverse-mode NCX current and stimulating ASMCs, whereas NK-1R antagonist decreased [Ca 2+ ]i in ASMCs by decreasing the reverse-mode NCX current to make ASMCs relax.