The action of forskolin (FSK), a stimulator of cAMP-dependent protein kinase (PKA), on nicotinic acetylcholine receptor-(nAChR-) channels was studied on cultured rat muscle fibres. The channel activity was estimated by determining Np, with N, being the number of channels and p, the single channel open probability. In order to elucidate the possible role of PKA in the modulation of nAChRs, FSK (10-50 microM) was added to the bath or to the pipette filling solution in the cell-attached configuration. The first protocol used was to test for indirectly-mediated cytosolic effects, the other, for any direct effects of the drug on nAChR-channels. Using both experimental protocols, no effects on the duration of single-channel openings or conductance were observed, while channel activity was significantly reduced. In particular, FSK 10 microM caused a reduction of Np only when applied to the non-patch membrane. FSK at higher concentrations, produced a more marked decrease of Np when present in the recording pipette. The present work provides evidence that the channel activity of muscle embryonic-type nAChRs can be influenced by a direct action of FSK, and is also significantly reduced by an indirectly-mediated cytosolic mechanism triggered by FSK.