CORTICOSTEROID RECEPTOR-DEPENDENT MODULATION OF CALCIUM CURRENTS IN RAT HIPPOCAMPAL CA1 NEURONS

Pyramidal CA1 neurons in the rat hippocampus contain mineralocorticoid (MRs) and glucocorticoid receptors (GRs) for corticosterone, which, in activated form, act as transcription factors of the genome. The relative MR and GR occupation changes throughout the day, with predominant MR occupation under rest in the morning and additional GR occupation in the evening and after stress. We examined the effect of MR and GR activation on Ca currents in hippocampal slices from adrenalectomized (ADX) rats under whole-cell voltage-clamp conditions. In slices from ADX rats, where MRs and GRs are unoccupied, Ca currents (particularly in the low-voltage range) were larger than in neurons from the sham-operated controls; these effects became apparent with a delay of greater than or equal to 3 days after ADX. Selective occupation of MRs in tissue from ADX rats greatly (by 70%) and persistently (up to 3 h) reduced transient but also sustained Ca conductances. Voltage dependency and kinetic properties of the currents were not affected. Occupation of GRs as well as MRs by corticosterone (30 nM) resulted in relatively large Ca currents, comparable to those recorded in tissue from mildly stressed sham-operated control animals. Interestingly, exclusive occupation of GRs with 30 nM RU 28362 was not sufficient to induce large Ca currents. The data suggest that the changes in MR and GR occupation throughout the day, related to circadian and stress-induced corticosterone release, are linked to marked alterations in Ca currents, with small Ca currents in the morning and large currents in the evening or after stress, Corticosteroid hormones may, thus, exert a persistent gene-mediated control over Ca conductances in the brain, affecting the excitability of neurons.