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 macroscopic currents in an outside-out patch-clamp configuration. Normal ACh receptors desensitized with a fast (6 ms) and slow time constant (104 ms). There was no significant difference in the current decay time between normal ACh receptors and mutant ACh receptors that possibly mimics PKC phosphorylation of the receptors. The selective PKC inhibitor, PKCl, prolonged the rate of desensitization of normal ACh receptors, and the similar effect was obtained with mutant ACh receptors lacking PKC phosphorylation sites. Phosphorylation of normal ACh receptors by the catalytic subunit of PKA or mutant ACh receptors that possibly mimic PKA phosphorylation of the receptors increased the rate of desensitization, but, in contrast, the receptors lacking PKA phosphorylation sites prolonged the current decay time. The results of the present study demonstrate that PKC or PKA phosphorylation of ACh receptors accelerates the rate of desensitization.
Nishizaki
T
T
Department of Physiology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. tomo@med.kobe-u.ac.jp
Sumikawa
K
K
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014101:Torpedo
D011978:Receptors, Nicotinic; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C