Human Isolated Bronchial Smooth Muscle Contains Functional Ryanodine/Caffeine–sensitive Ca-Release Channels

Human bronchial smooth muscle (HBSM) contraction is implicated in a variety of respiratory diseases, including asthma. Yet, the presence of an operative calcium-induced calcium release (CICR) mechanism, identified in various smooth muscles, has not been established in HBSM. We therefore studied Ca-releasing mechanisms in HBSM obtained at thoracotomy with special attention to ryanodine-sensitive receptor channels (RyRs). In freshly isolated bronchial myocytes, ryanodine (0.5 to 50 μ M) and caffeine (1 to 25 mM) induced transient increases in the cytoplasmic calcium concentration ([Ca2 +]i). Higher ryanodine concentrations ( > 100 μ M) inhibited the caffeine-induced [Ca2 +]i response, which was also blocked in the presence of tetracaine (300 μ M) or ruthenium red (200 μ M), two potent CICR inhibitors. In HBSM strips, caffeine induced a transient contraction which, likewise, was inhibited by ryanodine and tetracaine. However, ryanodine (200 μ M) modified neither the [Ca2 +]i response nor the contraction indu...