POSTNATAL DEVELOPMENTAL CHANGES OF AIRWAY SMOOTH MUSCLE

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Pulmonary disease is relatively common in the neonatal period, especially in those born prematurely. Bronchodilator therapy is beneficial in chronic lung diseases of infancy, suggesting an important role of airway smooth muscle in this prevalent and serious condition. It is known that the cellular function of airway smooth muscle is quite different in the fetus than in the adult and we suggest that the transition between these conditions extends for some time after birth. We have obtained data in a pig model which demonstrate striking differences between tracheal smooth muscles of newborn and adult animals with regard to 1) contractile sensitivity to K+ channel blockers and 2) the relationship between intracellular free Ca2+ concentration and tension. Our results are consistent with the general hypothesis that airway smooth muscle undergoes a transition from a phasic to a tonic muscle, beginning before birth but continuing into early childhood. Residual phasic characteristics may predispose to bronchospasm. We therefore proposed to characterize changes with age in Ca2+ homeostasis of airway smooth muscles obtained from pigs and humans. Our aims are to determine the cellular basis for developmental mechanisms involved in postnatal changes in contractile Ca2+ sensitivity, and to characterize the time course of postnatal changes in Ca2+ homeostasis in both pigs and humans. These studies will provide information regarding age-related changes in airway function that is important for understanding the unique pulmonary diseases of early childhood. Our results may suggest more effective approaches to the therapy or prevention of bronchospastic conditions of infancy.