Nicotinic receptors are regulated by protein kinase C activated via a nicotinic receptors-mediated signaling pathway.

The present study was conducted to examine the effect of protein kinase C (PKC) on nicotinic acetylcholine (ACh) receptors expressed in Xenopus oocytes by monitoring single-channel currents. In an outside-out patch-clamp configuration, ACh (1 microM) elicited single channel currents with a slope conductance of 31 pS (control) in normal Torpedo ACh receptors. Activation of PKC via an endogenous phosphatidylinositol signaling pathway elevated the slope conductance to 41 pS, which effect was blocked by the selective PKC inhibitor, staurosporine. Mutant ACh receptor channels, which mimic PKC phosphorylation of the receptors, exhibited a slope conductance of 41 pS. Notably, pretreatment with a higher concentration of ACh (100 microM) caused an increase in the slope conductance of the channels for 1 microM ACh (43 pS), which was the same level as obtained with either PKC activation or mutant ACh receptors, and this effect was also inhibited by staurosporine. In addition, the control slope conductance was reduced by PKC inhibitor peptide (24 pS), which corresponded to that obtained with another mutant ACh receptors lacking PKC phosphorylation sites (18 pS). Mouse muscle ACh receptors were also regulated by the same mechanism. The results of the present study suggest that ACh activates PKC via nicotinic ACh receptors, which alternatively, modulates the properties of the receptor channels.