Calcium, the control of smooth muscle function and bronchial hyperreactivity.
The Ca2+ requirements for excitation-contraction coupling in smooth muscle may be satisfied from both intracellular and extracellular sources, the relative extent of use of which is both tissue- and stimulant-dependent. Extracellular Ca2+ is apparently mobilized through two separate pathways, receptor operated (ROC) and potential dependent (PDC) Ca2+ channels. The latter process is sensitive to the Ca2+-channel antagonists, a heterogeneous group of compounds including verapamil, nifedipine and diltiazem. Ca2+ mobilization in respiratory smooth muscle is reviewed. The available evidence for this multiple stimulant-sensitive system indicates that both intra- and extracellular sources of Ca2+ are used. Data from bovine, canine and guinea pig tracheal muscle indicate, from studies of Ca2+-dependence of response and Ca2+ channel antagonist sensitivity, that the extent of use of extracellular Ca2+ lies in the order K+ greater than histamine greater than or equal to 5-hydroxytryptamine greater than acetylcholine. The bronchodilator activity of the Ca2+ channel antagonists is noted. Bronchial hyperreactivity is characterized by an increased sensitivity to a variety of stimulants including cold air, exercise, histamine and acetylcholine. The possible origins of this defect are noted. It is suggested that a defect in Ca2+ mobilization or in the receptor - Ca2+ mobilization coupling process at the level of the smooth muscle may constitute an important underlying cause of bronchial hyperreactivity. Potential analogies to reactivity changes seen in hypertensive vascular smooth muscle are noted.
D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D002118:Calcium / Q000502:physiology*; D004285:Dogs; D007473:Ion Channels / Q000502:physiology; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects
D007473:Ion Channels; D002118:Calcium