Am. J. Respir. Crit. Care Med., Volume 162, Number 2, August 2000, 687-694

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

JEAN-MARC HYVELIN, CÉCILE MARTIN, ETIENNE ROUX, ROGER MARTHAN, and JEAN-PIERRE SAVINEAU

Laboratoire de Physiologie Cellulaire Respiratoire INSERM (E 9937), Université Bordeaux 2, Bordeaux, France; and Molecular Endocrinology, Molecular Medicine Center, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom

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 µM) and caffeine (1 to 25 mM) induced transient increases in the cytoplasmic calcium concentration ([Ca²⁺]_i). Higher ryanodine concentrations (> 100 µM) inhibited the caffeine-induced [Ca²⁺]_i response, which was also blocked in the presence of tetracaine (300 µM) or ruthenium red (200 µM), two potent CICR inhibitors. In HBSM strips, caffeine induced a transient contraction which, likewise, was inhibited by ryanodine and tetracaine. However, ryanodine (200 µM) modified neither the [Ca²⁺]_i response nor the contraction induced by K⁺-rich (110 mM) solution. Reverse transcriptase/polymerase chain reaction (RT-PCR) and RNase protection assay performed in HBSM have revealed the existence of mRNAs encoding only the type 3 RyR. We also characterized acetylcholine-induced [Ca²⁺]_i and contractile responses. None of these responses was altered by ryanodine or by tetracaine. These results demonstrate, for the first time, the existence of functional RyRs in HBSM cells which, owing to the type of isoform or the amount of protein expressed, are not involved, under physiologic conditions, in depolarization- or agonist-induced contraction.

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