Calcium-channel blockers and asthma.

EditorialCalcium-channel blockers and asthma The concentration of free calcium ions (Ca++) in the cytoplasm regulates many aspects of cell function, including muscle contraction and the secretion of mediators, neurotransmitters and hormones.Con- traction of airway smooth muscle, secretion of mast cell mediators and mucus, and vagal neurotransmis- sion, all of which may be increased in asthma, are dependent on movement of Ca++ into the cell.This raises the possibility that an increase in Ca++ flux may be a fundamental abnormality in asthma and might be an explanation for bronchial hyperreactivity.'The development of drugs that interfere with the entry of Ca++ into cells has now made it possible to study the role of Ca++ in disease, and these drugs are widely used in the treatment of cardiovascular disease.There has recently been increasing interest in the use of calcium-channel blockers in asthma, not because of their therapeutic potential but because of what they may reveal about underlying mechanisms. CALCIUM IONS AND CELL FUNCTIONThe concentration of free intracellular Ca++ in rest- ing cells is approximately 0-1 ,moIIl, whereas that in extracellular fluid is 1 mmo0l/;2 3 and recent studies using bioluminescent indicators of free intracellular Ca++ have found that the Ca++ concentration increases 100-fold after cell activation.45When intracellular Ca++ rises to a critical concentration (about 1 ,umol/l) it binds to a specific binding protein called calmodulin, which then activates the specific kinase and enzyme system that brings about the response, such as contraction or secretion.This increase in cytoplasmic Ca++ is derived from extracellular Ca`+ or intracellular stores (mainly sarcoplasmic reticulum), or both.Indeed, the entry of Ca++ into the cell may trigger the release of Ca++ from intracellular stores.The source of Ca++ required for the cellular response may differ from tissue to tissue.The cell membrane itself is impermeable to Ca++ and Ca++ moves into the cell through specific channels.These are macromolecular structures traversing the membrane