[Ca2+]i oscillations induced by bradykinin in rat glioma cells associated with Ca2+ store-dependent Ca2+ influx are controlled by cell volume and by membrane potential.
Long-term superfusion with bradykinin causes oscillations of cytosolic Ca2+ activity ([Ca2+]i) in Fura-2 loaded rat glioma cells. The [Ca2+]i rise is associated with synchronous plasma membrane hyperpolarization oscillating with a frequency of 0.8-1.8 per min. The initial large transient [Ca2+]i rise, induced immediately with bradykinin admission results from InsP3-mediated Ca2+ release, whereas the subsequent oscillations depend mainly on Ca2+ influx, as demonstrated: (i) by blockade of [Ca2+]i oscillations by reduction of [Ca2+]ex' or addition of Ca(2+)-channel blockers; and (ii) evidence from Mn2+ quench experiments. Suppression of [Ca2+]i oscillations with high K+ depolarization and with block of Ca(2+)-dependent K+ channels proves that membrane hyperpolarization is required for Ca2+ influx during the oscillation. Ca2+ release from intracellular stores by inhibitors of endoplasmic reticulum Ca(2+)-ATPase attenuates or blocks the [Ca2+]i oscillations. This suggests that bradykinin-induced Ca2+ influx is controlled by the filling state of the stores. The [Ca2+]i oscillations are suppressed by hypertonic medium and enhanced by hypotonic medium. Cell swelling enhances Ca2+ influx. We propose the following model for generation of the oscillations in the glial cell line: InsP3-induced Ca2+ release from internal stores periodically evokes Ca2+ influx through Ca(2+)-permeable cation channels. Hyperpolarization of the plasma membrane due to the activation of Ca(2+)-dependent K+ channels enhances the Ca2+ influx. The concomitant K+ efflux could lead to cell shrinkage which suppresses Ca2+ influx. Cell volume and membrane potential probably serve as feedback regulators during the [Ca2+]i oscillations.
Reetz
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Institut für Neurobiochemie, Medizinischen Fakultät, Otto-von-Guericke-Universität Magdeburg, Germany.
Reiser
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D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009995:Osmosis; D051381:Rats; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D013729:Terpenes; D019284:Thapsigargin; D001920:Bradykinin; D002118:Calcium