Sensitivity and Specificity of Ca2+ Oscillations

Airway epithelial cells in culture displayed a wide range of sensitivities to extracellular ATP. This sensitivity is based on the Ca2+ response and can be classed in to three groups: low, intermediate and  high sensitivity.
 
 Low Sensitivity Cells: 5 uM ATP invokes only an initial Ca2+ transient (below, left, top trace). However, increasing doses of ATP, up to 100 uM, can evoke Ca2+ oscillations. The frequency of the oscillations increases with ATP concentration.
High Sensitivity Cells: A similar range of Ca2+ responses were observed in the high sensitivity cells. However, in these cells, the basic response of a single Ca2+ spike was evoked by 0.1 uM ATP while the fastest Ca2+ oscillations were evoked by 1 uM ATP. ATP doses of > 5 uM induced a plateau increase in Ca2+ .

Sensitivity to ATP and  UTP
Airway epithelial cells show similar Ca2+ responses to extracellular UTP. However, for all the cells examined, individual cells were more sensitive to UTP  than ATP. The graph (right) shows the responses of 3 different cells to 0.1 uM UTP (Red trace) or ATP (Yellow trace). In a low sensitivity cell (top) UTP, but not ATP, induced a single Ca2+ spike.  In an  intermediate sensitivity cell (middle), UTP induced a single Ca2+ oscillation while ATP induce only a Ca2+ spike. In a high sensitivity cell (bottom), UTP induced Ca2+ oscillations with a frequency greater than those induced by ATP.

 

Conclusion
The Ca2+ responses induced in airway epithelial cells by ATP and UTP and the greater sensitivity of these responses to UTP as compared to ATP suggests that the Ca2+ responses are mediated via a P2U receptor.

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