Ca2+-signaling in airway smooth muscle cells is altered in T-bet knock-out mice

• Published in: Respiratory research 2006-02, Vol.7 (1), p.33-33, Article 33
• Main Authors: Bergner, Albrecht, Kellner, Julia, Silva, Anita Kemp da, Gamarra, Fernando, Huber, Rudolf M
• Format: Article
• Language: English
• Subjects: Acetylcholine; Analysis; Animals; Asthma; Bank clearinghouses; Calcium Signaling - physiology; Cells, Cultured; Homeostasis - physiology; Lung - physiology; Mice; Mice, Inbred BALB C; Mice, Knockout; Myocytes, Smooth Muscle - physiology; Smooth muscle; T-Box Domain Proteins; Transcription Factors - deficiency; Transcription Factors - genetics
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/1465-9921-7-33

Airway smooth muscle cells (ASMC) play a key role in bronchial hyperresponsiveness (BHR). A major component of the signaling cascade leading to ASMC contraction is calcium. So far, agonist-induced Ca2+-signaling in asthma has been studied by comparing innate properties of inbred rat or mouse strains, or by using selected mediators known to be involved in asthma. T-bet knock-out (KO) mice show key features of allergic asthma such as a shift towards TH2-lymphocytes and display a broad spectrum of asthma-like histological and functional characteristics. In this study, we aimed at investigating whether Ca2+-homeostasis of ASMC is altered in T-bet KO-mice as an experimental model of asthma. Lung slices of 100 to 200 microm thickness were obtained from T-bet KO- and wild-type mice. Airway contraction in response to acetylcholine (ACH) was measured by video-microscopy and Ca2+-signaling in single ASMC of lung slices was assessed using two-photon-microscopy. Airways from T-bet KO-mice showed increased baseline airway tone (BAT) and BHR compared to wild-type mice. This could be mimicked by incubation of lung slices from wild-type mice with IL-13. The increased BAT was correlated with an increased incidence of spontaneous changes in intracellular Ca2+-concentrations, whereas BHR correlated with higher ACH-induced Ca2+-transients and an increased proportion of ASMC showing Ca2+-oscillations. Emptying intracellular Ca2+-stores using caffeine or cyclopiazonic acid induced higher Ca2+-elevations in ASMC from T-bet KO- compared to wild-type mice. Altered Ca2+-homeostasis of ASMC contributes to increased BAT and BHR in lung slices from T-bet KO-mice as a murine asthma model. We propose that a higher Ca2+-content of the intracellular Ca2+-stores is involved in the pathophysiology of these changes.