Summary
The effect of the calcium entry blocker flunarizine on a high-potassium induced increase of intracellular free calcium was studied. The experiments were done with neurons isolated from rat dorsal root ganglia and loaded with the calcium-sensitive dye fura-2. The increase of calcium induced by 60 mmol/1 potassium was abolished after removal of extracellular calcium, was reversibly reduced by 50 μmol/l cadmium (76% inhibition), 50 μmol/1 nickel (25% inhibition) and 10 μmol/1 nifedipine (18°10 inhibition), and reversibly increased after removal of extracellular sodium (26% increase). The potassium induced increase of intracellular calcium is, therefore, mediated by transmembrane calcium influx, probably to a large extent through cadmium-sensitive calcium channels. Flunarizine (5 min incubation followed 1 min wash-out) reduced the amplitude of the high-potassium induced calcium increase in a dose-dependent manner (K d = 370 ± 100 nmol/l; mean ± SEM; n = 8), causing complete inhibition at a concentration of 10 μmol/1 in the majority of cells. Flunarizine (≥ 1 μmol/1) caused a reversible increase of the resting level of intracellular calcium in some cells, an effect which disappeared in the absence of extracellular calcium. The drug (1 μmol/1 had no influence on the time course of recovery of intracellular calcium subsequent to a rise induced by high-potassium or by the calcium ionophore A23187. It is concluded that flunarizine acts as an inhibitor of depolarization-mediated calcium influx. At a concentration of 1 μmol/1, the drug presumably has no effect on cellular calcium extrusion and/or sequestration mechanisms.
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Leybaert, L., De Ley, G. & de Hemptinne, A. Effects of flunarizine on induced calcium transients as measured in fura-2-loaded neurons of the rat dorsal root ganglion. Naunyn-Schmiedeberg's Arch Pharmacol 348, 269–274 (1993). https://doi.org/10.1007/BF00169155
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DOI: https://doi.org/10.1007/BF00169155