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

ABSTRACT

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.