Modulation of amino acid-gated ion channels by protein phosphorylation

Abstract

The major excitatory and inhibitory amino acid receptors in the mammalian central nervous system are considered to be glutamate, gamma-aminobutyric acid type A (GABAA), and glycine receptors. These receptors are widely acknowledged to participated in fast synaptic neurotransmission, which ultimately is responsible for the control of neuronal excitability. In addition to these receptors being regulated by endogenous factors, including the natural neurotransmitters, they also form target substrates for phosphorylation by a number of protein kinases, including serine/threonine and tyrosine kinases. The process of phosphorylation involves the transfer of a phosphate group(s) from adenosine triphosphate to one or more serine, threonine, or tyrosine residues, which are invariably found in an intracellular location within the receptor Phosphorylation is an important means of receptor regulation since it represents a covalent modification of the receptor structure, which can have important implications for ion channel function. This chapter reviews the current molecular and biochemical evidence regarding the sites of phosphorylation for both native neuronal and recombinant glutamate, GABAA and glycine receptors, and also reviews the functional electrophysiological implications of phosphorylation for receptor function.