EFFECTS OF PKC AND PKA PHOSPHORYLATION ON DESENSITIZATION OF NICOTINIC ACETYLCHOLINE-RECEPTORS

The present study was designed to assess the effect of protein kinase C (PKC) and cAMP-dependent protein kinase (PKA) on desensitization of Torpedo acetylcholine (ACh) receptors by analyzing summated macroscopi c currents in an outside-out patch-clamp configuration. Normal ACh rec eptors desensitized with a fast (6 ms) and slow time constant (104 ms) . There was no significant difference in the current decay time betwee n normal ACh receptors and mutant ACh receptors that possibly mimics P KC phosphorylation of the receptors. The selective PKC inhibitor, PKCl , prolonged the rate of desensitization of normal ACh receptors, and t he similar effect was obtained with mutant ACh receptors lacking PKC p hosphorylation sites. Phosphorylation of normal ACh receptors by the c atalytic subunit of PKA or mutant ACh receptors that possibly mimic PK A phosphorylation of the receptors increased the rate of desensitizati on, but, in contrast, the receptors lacking PKA phosphorylation sites prolonged the current decay time. The results of the present study dem onstrate that PKC or PKA phosphorylation of ACh receptors accelerates the rate of desensitization. (C) 1998 Elsevier Science B.V. All rights reserved.