Single type-2 astrocytes show multiple independent sites of Ca2+ signaling in response to histamine

Intracellular Ca2+ plays an important role in signal transduction as a second messenger. In various types of cells, inositol 1,4,5-trisphosphate-induced elevations of intracellular free Ca2+ concentration ([Ca2+]i) have been reported to be uniform in single cells or originate at discrete sites from which they then propagate throughout the cells. These observations so far imply that a single cell functions as a minimal unit for inositol 1,4,5-trisphosphate-induced Ca2+ signaling. In this study, we examined the effects of histamine on [Ca2+]i of type-2 astrocytes using fura-2-based digital imaging fluorescence microscopy and found an unusual type of Ca2+ signaling in these cells. Histamine induced [Ca2+]i elevation in type-2 astrocytes by means of histamine H1 receptors. Submaximal concentrations of histamine (10(-7)-10(-6) M) evoked multiple sites of oscillatory [Ca2+]i elevation in single type-2 astrocytes. These Ca2+ "hot spots" were localized in the processes of the astrocytes but not in the cell bodies. The time courses of [Ca2+]i oscillations in different hot spots were not synchronized, indicating that each of them formed an independent compartment of Ca2+ signaling. When higher concentrations (10(-5)-10(-4) M) of histamine were added, [Ca2+]i in the processes remained elevated at high levels and [Ca2+]i elevations propagated from the processes to the cell bodies. These results suggest that individual processes of type-2 astrocytes can form minimal units for Ca2+ signaling in response to submaximal concentrations of histamine and that single type-2 astrocytes may function as multiple units for Ca2+ signaling.