Regulation of the Nicotinic Acetylcholine Receptor Channel by Protein Phosphorylatio

Protein phosphorylation is one of the major regulatory mechanisms in the control of cellular metabolism and plays an important role in the regulation of ion channel function. The nicotinic acetylcholine receptor has been an excellent model system to study in detail the regulation of ion channels by protein phosphorylation. The nicotinic acetylcholine receptor is a multisubunit (α₂βγδ) neurotransmitter-dependent ion channel that has been shown to be phosphorylated on seven different sites by three different protein kinases in postsynaptic membranes isolated from Torpedo californica. Cyclic adenosine 3’,5’-cyclic monophosphate (cAMP)-dependent protein kinase phosphorylates the γ- and δ-subunits, protein kinase C phosphorylates the δ- and α-subunits, and the tyrosine-specific protein kinase phosphorylates the β-, γ-, and δ-subunits of the receptor. Phosphorylation of the γ- and δ-subunits of the purified nicotinic receptor by purified cAMP-dependent protein kinase in vitro dramatically increases the rate of desensitization of the receptor.