19] Protein phosphorylation of ligand-gated ion channels

Abstract

Publisher Summary Neurotransmitter receptors mediate signal transduction at the postsynaptic membrane of chemical synapses in the nervous system. The major excitatory and inhibitory neurotransmitter receptors in the brain are ligandgated ion channels. These receptors directly bind neurotransmitters, resulting in the opening of an intrinsic ion channel. The predominant ligand-gated ion channels in the nervous system are the nicotinic acetylcholine receptor, the glutamate receptors, the γ-aminobutyric acid (GABA A ) receptors and the glycine receptors. Biochemical and electrophysiologic studies of these receptors have demonstrated that they are multiply phosphorylated by a variety of protein kinases. Phosphorylation of these receptors regulates many functional properties, including desensitization, open channel probability, open time, and subcellular targeting. Because of the central role of ligand-gated ion channels in synaptic transmission, protein phosphorylation of these receptors is a major mechanism in the regulation of synaptic transmission and may underlie many forms of synaptic plasticity. This chapter reviews a variety of techniques to examine the role of protein phosphorylation in the regulation of ligand-gated ion channel function. The chapter also reviews general strategies and methods for characterizing the phosphorylation state of ligand-gated ion channels, identifying phosphorylation sites on these channels, and analyzing the physiologic consequences of channel phosphorylation.