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.