This study evaluated the relationship between regional elevation in intracellular calcium concentration ([Ca2+](i)) induced by acetylcholine (ACh) and the global cellular responses in porcine tracheal smooth muscle (TSM) cells. Regional (~1.5 μm3) and global (whole cell) changes in [Ca2+](i) were measured in fluo-3 loaded TSM cells using real-time confocal microscopy. Regional responses appeared as propagating [Ca2+](i) oscillations whereas global responses reflected the spatiotemporal integration of these regional responses. Within a region, [Ca2+](i) oscillations were 'biphasic' with initial higher frequencies, followed by slower steady-state oscillations. With increasing ACh concentration, the peak (maximum value relative to 0 nM) of regional [Ca2+](i) oscillations remained relatively constant, whereas both frequency and propagation velocity increased. In contrast, the global spatiotemporal integration of the regional oscillatory responses appeared as a concentration-dependent increase in peak as well as mean cellular [Ca2+](i). We conclude that the significance of ACh-induced [Ca2+](i) oscillations lies in the establishment of mean [Ca2+](i) level for slower Ca2+-dependent physiological processes via modulation of oscillation frequency and propagation velocity. (C) 2000 Harcourt Publishers Ltd.
Bibliographical noteFunding Information:
The authors thank Mr Thomas Keller for his technical assistance in cell preparation. This research was supported by a fellowship from Abbott Laboratories to CMP, and NIH grants HL 057498 (MSK), GM 56686 (GCS), and the Mayo Foundation.