S100 calcium binding protein affects neuronal electrical discharge activity by modulation of potassium currents

S100 calcium binding protein has been associated with a variety of intra- a nd extracellular calcium-mediated functions, including learning and memory. We have previously localized S100-immunoreactive neurons correlated with s pontaneous discharge activity in the central nervous system of the mollusc, Helix pomatia. In this study, we further investigated the effects of S100 (S100B and S100A1) on electrical discharge activity and membrane currents o f Helix neurons, using current- and voltage-clamp techniques. Extracellular application of disulphide-linked S100B (S100B-s-s) in pico- to nanogram/ml concentrations was found to hyperpolarize the membrane resting potential, to inhibit spontaneous discharge activity of action potentials, to after th e stimulus response behaviour from tonic to phasic, to decrease the duratio n and increase the afterhyperpolarization of action potentials, and to redu ce the cell input resistance. Measurement of membrane currents revealed tha t the total outward current was increased by S100B-s-s. Separation of outwa rd currents showed that three types of potassium currents were altered. (i) an inward rectifying current, (ii) a calcium-activated potassium outward c urrent, both increased by S100B-s-s, and (iii) a delayed, voltage-dependent potassium outward current which was decreased by the protein. The transien t potassium outward and the calcium inward currents were not affected by S1 00B-s-s. Immunocytochemistry showed intracellular labelling of the cytoplas m after extracellular application of the protein, indicating internalizatio n and suggesting an internal site of action. Injection of S100A1 mimicked t he effects of S100B-s-s on discharge activity and action potentials. We conclude from our experiments that S100 calcium binding protein, by modu lation of potassium currents, may play a role as a neuromodulator in nervou s functions. (C) 1999 IBRO. Published by Elsevier Science Ltd.