CORTICOSTEROID-MEDIATED MODULATION OF CARBACHOL RESPONSIVENESS IN CA1 PYRAMIDAL NEURONS - A VOLTAGE-CLAMP ANALYSIS

Pyramidal neurons in the rat hippocampal CA1 area contain mineralocorticoid (MRs) and glucocorticoid (GRs) receptors for corticosterone. Previous current clamp experiments showed that depolarizations evoked by carbachol (1-3 mu M) depend on relative MR/GR occupation: carbachol responses are small with predominant MR-activation and larger when both receptor types are occupied. Multiple K-conductances underlie the carbachol-induced depolarization. In the present study we used the single electrode voltage clamp technique to examine which K-conductances modulated by carbachol are sensitive to corticosteroid treatment in vitro. We observed that 1 mu M carbachol significantly reduced the I-K,I-Leak while the I-M was hardly affected; carbachol effects on the I-K,I-Leak were significantly reduced under conditions of predominant MR activation compared to simultaneous activation of MRs and GRs. With a higher (10 mu M) carbachol dose, steroid modulation of the I-K,I-Leak showed a similar tendency. The amplitude of the I-M was largely reduced by 10 mu M carbachol but appeared to be not affected by steroid treatment. We conclude that the previously described suppression of the carbachol-induced depolarization with predominant activation MRs is caused by an attenuation of the carbachol action on the I-K,I-Leak. (C) 1995 Wiley-Liss, Inc.