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⁺ histamine 5‐hydroxytryptamine > acetyl‐choline. 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.