Effects of latrunculin‐B in smooth muscle contraction, Ca2+ oscillations and Ca2+ sensitization in small intrapulmonary airways

Abstract

The role of actin filament dynamics in the regulation of airway smooth muscle contraction is not fully understood. We have investigated the effects of impairing actin filament polymerization with latrunculin‐B (Lat‐B) –a G‐actin binding toxin, on agonist‐induced Ca2+ signaling, Ca2+ sensitivity and contraction in small intrapulmonary airways in mouse lung slices. Incubation of lung slices with Lat‐B (0.1 μM) for 60 min caused a reduction of airway contraction induced by 0.1 μM serotonin (5‐HT) and 0.1 μM acetylcholine (ACh) by 54 ± 8% and 42 ± 6%, respectively. In addition, Lat‐B induced relaxation of airways pre‐contracted with agonists. Maximal airway relaxation was 55 ± 5% and 53 ± 8% in airways pre‐contracted with 5‐HT and ACh, respectively. Furthermore, Lat‐B affected the Ca2+ signaling induced by ACh and 5‐HT by reducing the frequency of agonists‐induced Ca2+ oscillations. Finally, in Ca2+ permeabilized lung slices, Lat‐B induced relaxation of airways pre‐contracted with either 5‐HT or ACh indicating Ca2+ desensitization. Together these results suggest that actin filament dynamics are important for the regulation of airway smooth muscle contraction and signaling.