THE NEUROSTEROIDS PREGNENOLONE AND PREGNENOLONE-SULFATE BUT NOT PROGESTERONE, BLOCK CA2+ CURRENTS IN ACUTELY ISOLATED HIPPOCAMPAL CA1 NEURONS

The neurosteroids pregnenolone (PE) and pregnenolone-sulfate (PS) have been shown to interact with the GABA(A) receptor in the central nervous system. In contrast, nothing is known of any possible modulation of voltage-gated calcium channels (VGCC). We have examined the interaction of PE, PS and progesterone on VGCC in acutely isolated adult guinea-pig hippocampal CA1 neurons using the whole-cell patch clamp technique. PE and PS depressed the calcium current at low micromolar concentrations (0.001 - 100-mu-M). The time to peak of the calcium current was slowed by PE and PS. The blocking action of PE and PS occurs in the presence of 10-mu-M picrotoxin. In contrast, progesterone had no effect on the Ca2+ current, indicating specificity for PE and PS. These results demonstrate a direct and novel membrane site of action for PE and PS, suggesting a possible role influencing brain excitability.