Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca2+ channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs) precontracted with acetylcholine (ACH). In the presence of nifedipine (10 µM), ACH induced cytosolic Ca2+ elevation and cell shortening in single airway smooth muscle cells (ASMCs), and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca2+-free conditions, and, following a restoration of Ca2+, a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs) were blocked by chloroquine. Pyrazole 3 (Pyr3), an inhibitor of transient receptor potential C3 (TRPC3) channels, partially inhibited ACH-induced contraction, intracellular Ca2+ elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.
Configuration systems are increasingly used as a means for efficient design of customized product service systems (PSS) to satisfy diverse customer needs. Cost evaluation is thereby important to assist the configuration engineers in making decisions on feasible configuration solutions. However, little research attention has been received until recently. To fill this gap, this paper contributes in developing a framework for cost evaluation in PSS configuration. A holistic view of PSS configuration, the three-dimensional PSS cost element, and a life cycle oriented cost evaluation approach are successively proposed. The framework is thereby established with a number of parts, including the preparatory stage, the evaluation stage and the configuration stage. A pump PSS is illustrated to validate the developed framework. Four feasible configuration solutions in one configuration activity are evaluated and compared. The configuration engineers are thus assisted with the decision on selecting the one with the least cost.
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