The significance of chloride in the inhibitory action of disodium cromoglycate on immunologically-stimulated rat peritoneal mast cells

Background: The microelectrode array (MEA) was used to investigate the pharmacological relevance of chloride (Cl(-)) ions in antigen-dependent mast cell activation and the inhibitory effect of disodium cromoglycate (DSCG) on mast cell activation. Methods: The movements of ions across the cellular membrane and the potential relationship between Cl(-) channels and DSCG during immunological activation were investigated using the MEA. The results were then subsequently compared with the amount of histamine released from anti-IgE activated peritoneal mast cells. Results: The inclusion of charybdotoxin (ChTX) in CL-free buffer showed that the measured field potentials during antigen-stimulated peritoneal mast cell were a combination of Cl(-) influx and K(+) efflux. The delayed onset time of Cl(-) influx indicated the presence of a delayed outwardly-rectifying Cl(-) current in the antigen-stimulated peritoneal mast cells. The use of 5-nitro-2-(3-phenylpropylamino) benzoic acid demonstrated that the activated mast cell membrane potential can be stabilised, thereby reducing the amount of histamine released from the anti-IgE activated mast cells. The correlation between the results of the histamine release assay and the electrophysiological measurements demonstrated the importance of Cl(-) to anti-IgE dependent mast cell activation. The inhibitory effect of DSCG on anti-IgE activated cells, however, did not correlate with the presumed influx of Cl(-). Conclusions: The MEA data suggest that Cl(-) influx is crucial to IgE-dependent mast cell degranulation. General significance: While the MEA cannot yield information about single channel properties, it is convenient to use and can provide information on the global changes in electrophysiological responses of non-excitable cells. (C) 2011 Elsevier B.V. All rights reserved.