The pathogenesis of cystic fibrosis: a proposal for calmodulin as the basic biochemical defect.

In cystic fibrosis (CF) there are two major defects which lead to most clinical manifestations of the disease. These are the electrolyte sweat defect and the abnormality of mucous secretions. Both may be satisfactorily explained by increased intracellular Ca++. In Na+ reabsorbing cells, such as exocrine sweat glands, increased Ca++ inhibits transepithelial Na+ transport. In mucus-secreting cells, high Ca++ levels may lead to physiochemical changes in secreted mucus. Increased intracellular Ca++ levels are hypothesized to be caused either by a defective Ca++ efflux cellular mechanism, or by increased intracellular binding of Ca++.