Airway smooth muscle.

The greatest impetus to research in elucidating the fundamental biophysics and biochemistry of airway smooth muscle (ASM) has undoubtedly been provided by the need to understand how these are altered in asthma. Many of the biophysical and biochemical properties of this muscle have been reviewed before (Stephens, 1970; Stephens, 1977; Mulvaney, 1979; Souhrada and Loader, 1979; Stephens and Kroeger, 1980). They resemble those of striated muscle; however, even though mechanical properties are very similar, there are differences in biochemistry. For example, in smooth muscle, calcium-sensitive regulation of contraction is mediated by a calmodulin/myosin-light-chain kinase/phosphatase system, not by the familiar troponin-tropomyosin system (Gorecka et al., 1974; Mrwa and Ruegg, 1975; Dillon et al., 1981; Aksoy et al., 1982). Thus, the molecular mechanisms to be investigated in understanding disorders of increased smooth muscle contraction, which occur in allergic bronchospasm (Souhrada and Dickey, 1976), for example, may be quite different from those in striated muscle. Much of the following material is based on studies of canine tracheal smooth muscle (TSM) because there is evidence (Jenne et al., 1975) that it serves as a model for ASM-at least with respect to contractility down to the sixth generation of airways. Studies of isolated smooth muscle from smaller airways (Russell, 1978) are few and are based mainly on studies of lung strips (Lulich et al., 1976). Since then, we have developed a bronchial smooth muscle preparation (fifth generation) that allows precise study of those airways that are involved in allergic bronchospasm. Considerable work has been carried out on ASM from a variety of animal models of asthma. It should be pointed out that none of these reproduces the human disease exactly, and that they really should be identified as examples of nonspecific hyperreactivity. Be that as it may, the nonspecificity found in human patients in vivo and in animals (Peterson et al., 1971; Hargreave et al., 1980) suggests that the primary cause of asthma may reside at the muscle cell level. Whether it is the cell membrane, the excitation-contraction coupling apparatus, or the contractile machinery that is primarily involved, is not yet known with certainty.