The regulatory influence of bradykinin and inositol-1,4,5-trisphosphate on the membrane potential in neural cell lines.
The effect of bradykinin on membrane potential, level of cyclic nucleotides and of cytosolic Ca2+-activity was determined in neural cell lines. Bradykinin induced a transient hyperpolarization followed by a depolarization in mouse neuroblastoma x rat glioma hybrid cells and in polyploid rat glioma cells. The reversal potential of the hyperpolarizing response depended on the extracellular K+ concentration. The K+ channel blockers, Ba2+, quinidine, and 4-aminopyridine, inhibited the response to bradykinin. This suggests that the hyperpolarization of ca. 1 min duration, which was accompanied by a decreased input resistance, is due to activation of K+ channels. Upon addition of bradykinin to the cells the cytosolic Ca2+-activity increased transiently. Ca2+ was involved in the induction of the hyperpolarization by bradykinin, since both removal of extracellular Ca2+ and injection of EGTA into the cells suppressed the membrane potential response. Bradykinin induced the formation of inositol-1,4,5-trisphosphate (IP3), an agent known to release Ca2+ from intracellular stores, and stimulated the uptake of 45Ca2+ into the cells. Therefore the increased level of intracellular Ca2+ activating the K+ conductance could be due to two components: release from intracellular pools and uptake. IP3 seems to be involved in the membrane potential response, because intracellular injection of either IP3 or Ca2+ into the glioma cells elicited a hyperpolarizing response which resembled that after application of bradykinin and was also susceptible to the K+ channel blocking agents listed above. However, the formation of cyclic GMP by bradykinin apparently plays no role in the membrane potential effect of bradykinin.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005910:Glioma / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D013403:Sugar Phosphates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007295:Inositol Phosphates; D007473:Ion Channels; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D006152:Cyclic GMP; D011188:Potassium; D001920:Bradykinin; D002118:Calcium