Bradykinin induces hyperpolarizations in rat glioma cells and in neuroblastoma X glioma hybrid cells.

The effect of the nonapeptide bradykinin on the membrane potential of permanent cell lines from neural origin was studied. A hyperpolarizing response of 10-30 s duration was produced when bradykinin was iontophoretically applied onto polyploid rat glioma cells (clone C6-4-2). Starting from the resting membrane potential the peak value of the hyperpolarizing response was reached within 0.5-1.5 s. Then the potential returned more slowly to the original value. The hyperpolarization was associated with an approximately 50% decrease in membrane resistance. Neither Na+ nor Cl- seemed to be important for the hyperpolarizing response, since bradykinin elicited similar hyperpolarizations in cells exposed to media in which Na+ or Cl- were replaced by choline or isethionate, respectively. Ca2+ fluxes are unlikely to be involved, since the addition of D600 did not affect the hyperpolarizations induced by bradykinin. However, a 10-fold increase in the concentration of K+ in the medium reduced the amplitude of the hyperpolarization by 40 mV. Thus, the hyperpolarization induced by bradykinin is associated with decrease in membrane resistance which is likely to be caused by an increased K+-conductance. The glioma cells showed a desensitization upon repeated application of bradykinin. However, the sensitivity of the cells to bradykinin was restored after 3-8 min of incubation in the absence of bradykinin. Since an antagonist of bradykinin is not known, the specificity of the action of bradykinin is difficult to assess. Nevertheless, the hyperpolarizing response to bradykinin appears to be specific insofar as other peptides, i.e. lutoliberin, thyroliberin, neurotensin, substance P and apamin, exerted no effect on the membrane potential of the glioma cells. Bradykinin-elicited hyperpolarizations with characteristics similar to those described above could also be demonstrated in neuroblastoma X glioma hybrid cells, but not in multinucleated fibroblast cells.