Secretion in alveolar type II cells at the interface of constitutive and regulated exocytosis

Long-term, simultaneous, measurements of cytoplasmic free Ca2+ concentratio ns and single exocytotic fusion events in surfactant-secreting type II cell s were performed. All fusion (constitutive, phorbol ester-induced, and agon ist-induced) was Ca2+-dependent. Kinetic analysis revealed that agonist (ad enosine triphosphate [ATP])-induced fusion exhibited a kinetic pattern that correlated well with the Ca2+ signal. The effects of Ca2+ release from int racellular stores (early) and Ca2+ entry (late) could be demonstrated for t he first time by dissecting the slow (10-to-15-min) fusion response to ATP into these two components. Bath Ba2+ or Sr2+ could replace Call to elicit a fusion response in thapsigargin-pretreated cells lacking ATP-induced Ca2release from stores. Although the late response was partially inhibited by interrupting the phospholipase D-protein kinase C axis, a high Ca2+ depende nce of the entire secretory course was demonstrated by a significant correl ation between the integrated Ca2+ signal and the fusion response. There was also a highly significant correlation between constitutive and ATP-stimula ted fusion activity in individual cells. We propose a common mechanistic mo del for all types of fusion in this slow secretory cell, in which constitut ive and regulated forms of exocytosis are subject to the same principles of regulation.