FORSKOLIN REDUCES THE ACTIVITY OF THE RAT MUSCLE EMBRYONIC TYPE ACETYLCHOLINE-RECEPTOR CHANNEL

The action of forskolin (FSK), a stimulator of cAMP-dependent protein kinase (PKA), on nicotinic acetylcholine receptor- (nAChR-) channels w as studied on cultured rat muscle fibres. The channel activity was est imated by determining Np, with N, being the number of channels and p, the single channel open probability. In order to elucidate the possibl e role of PKA in the modulation of nAChRs, FSK (10-50 mu M) was added to the bath or to the pipette filling solution in the cell-attached co nfiguration. The first protocol used was to test for indirectly-mediat ed 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, whil e channel activity was significantly reduced. In particular, FSK 10 mu M caused a reduction of Np only when applied to the non-patch membran e. FSK at higher concentrations, produced a more marked decrease of Np when present in the recording pipette. The present work provides evid ence that the channel activity of muscle embryonic-type nAChRs can be influenced by a direct action of FSK, and is also significantly reduce d by an indirectly-mediated cytosolic mechanism triggered by FSK.