Spontaneous calcium oscillatory patterns in mammotropes display non-randomdynamics

We previously showed that primary rat mammotropes exhibited four distinct p atterns of 'spontaneous' free intracellular calcium ([Ca2+](i)) oscillatory behavior: a quiescent state A and three oscillatory states B, C & D, which differed in frequency/amplitude characteristics. When [Ca2+](i) was monito red in 10 min windows separated by several hours, these phenotypes were fre quently found to interconvert, raising the question about whether these tra nsitions were random or ordered events. We reasoned that if such activity w ere random, then neither episode duration nor transitional probabilities sh ould differ among phenotypes. We tested this logic in the current study by making long-term, continuous measurements of [Ca2+](i) in mammotropes micro injected with Fura-2-dextran and identified by their ability to express a p rolactin promoter-driven reporter plasmid. We found that transitions occurr ed in similar to 25% of cells (n = 36 from 9 independent experiments) once every 1-5 h and demarcated phenotype episodes of different duration (A, 1.0 4 +/- 0.2 h; B, 1.64 +/- 0.3 h; C, 2.45 +/- 0.62 h; D, 0.90 +/- 0.2 h, mean i SEM). Moreover, some transitions occurred more frequently than others an d linked specific phenotypes into a common pattern: C to B to A. Our result s demonstrate that the seemingly spontaneous nature of [Ca2+](i) phenotype transitions are, in fact, ordered and support the view that they comprise a structured 'code' like that proposed to underlie calcium-dependent regulat ion of exocytosis and gene expression. (C) 2000 Harcourt Publishers Ltd.