Heterogeneity in cytosolic calcium responses to hypoxia in carotid body cells

Previous investigators have reported that intracellular pH responds to hypoxia with a heterogenous pattern in individual glomus cells of the carotid body. The aim of the present study was to examine whether hypoxia had similar effects on cytosolic calcium ([Ca2+](i)) in glomus cells, and if so, whether a heterogenous response pattern is also seen in other cell types. Experiments were performed on glomus cells from adult rat carotid bodies, rat pheochromocytoma (PC12) and vascular smooth muscle (A7r5) cells. Changes in [Ca2+](i) in individual cells were determined by fluorescence imaging using Fura-2. Glomus cells were identified by catecholamine fluorescence. [Ca2+](i) in glomus cells increased in response to hypoxia (pO(2) = 35 +/- 8 mmHg; 5 min), whereas hypoxia induced decreases in [Ca2+](i) were not seen. Increases in [Ca2+](i) were observed in 20% of the isolated cells and strings of cells, but clustered glomus cells never responded. The magnitude of the calcium change in responding cells was proportional to the hypoxic stimulus. Under a given hypoxic challenge, there were marked variations in the response pattern between glomus cells. The response pattern characteristic of any given cell was reproducible. At comparable levels of hypoxia, PC12 cells also responded with an increase in [Ca2+](i) with a heterogenous response pattern similar to that seen in glomus cells. In contrast, increases in [Ca2+](i) in A7r5 cells could be seen only with sustained hypoxia (similar to 20 min), and little heterogeneity in the response patterns was evident. These results demonstrate that: (a) hypoxia increases cytosolic calcium in glomus cells; (b) response patterns were heterogeneous in individual cells; and (c) the pattern of the hypoxia-induced changes in [Ca2+](i) is cell specific. These results suggest that hypoxia-induced increases in [Ca2+](i) are faster in secretory than in non-secretory cells.