Abstract
The effects of trifluoperazine hydrochloride (TFP), a calmodulin antagonist, on L-type Ca2+ currents (L-type ICa2+) and their Ca2+-dependent inactivation, were studied in identifiedHelix aspersa neurons, using two microelectrode voltage clamp. Changes in [Ca2+]i were measured in unclamped fura-2 loaded neurons. Bath applied TFP produced a reversible and dose-dependent reduction in amplitude of L-type ICa2+ (IC50=28 μM). Using a double-pulse protocol, we found that TFP enhances the efficacy of Ca2+-dependent inactivation of L-type ICa2+. Trifluoperazine sulfoxide (50 μM), a TFP derivative with low calmodulin-antagonist activity, did not have any effects on either amplitude or inactivation of L-type ICa2+. TFP (20 μM) increased basal [Ca2+]i from 147±37 nM to 650±40nM (N=7). The increase in [Ca2+]i was prevented by removal of external Ca2+ and curtailed by depletion of caffeine-sensitive intracellular Ca2+ stores. Since TFP may also block protein kinase C (PKC), we tested the effect of a PKC activator (12-O-tetradecanoyl-phorbol-13-acetate) on L-type Ca2+ currents. This compound produced an increase in L-type ICa2+ without enhancing Ca2+-dependent inactivation. The results show that 1) TFP reduces L-type ICa2+ while enhancing the efficacy of Ca2+-dependent inactivation. 2) TFP produces an increase in basal [Ca2+]i which may contribute to the enhancement of Ca2+-dependent inactivation. 3) PKC up-regulates L-type ICa2+ without altering the efficacy of Ca2+ dependent inactivation. 4) The TFP effects cannot be attributed to its action as PKC blocker.
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Cruzblanca, H., Gamiño, S.M., Bernal, J. et al. Trifluoperazine enhancement of Ca2+-dependent inactivation of L-type Ca2+ currents inHelix aspersa neurons. Invertebrate Neuroscience 3, 269–278 (1998). https://doi.org/10.1007/BF02577687
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DOI: https://doi.org/10.1007/BF02577687