Transmitter-Gated Channels in Nervous System

Overview of Transmitter-Gated Channels

The transmitter-gated ion channels form a class of multisubunit membrane-spanning receptors that are essential for rapid signal transduction. The property that defines this class is that the transmitter molecule itself operates the opening or closing of the channel by binding to a site on the receptor. These channels are one of several classes of the receptors now known to act in membrane signal transduction. This classification covers hundreds of receptor types that are concerned with signal transmission between neurons, between glia and neurons, or between neurons and muscles or other effector organs, as well as with the responses of glands and muscles to circulating signals.

Table 1 Transmitter-gated ion channels.

Structure of Transmitter-Gated Channels

Most structural and functional information is available for the nicotinic acetylcholine (ACh) receptor of skeletal muscles or electric organs and in this case, it has been definitively established that all of the subunits span the membrane, forming a pentamer that encloses a central ion channel. There are four subunit types, α, β, γ, and δ, which are in the stoichiometry α₂βγδ. Interestingly, a cation channel within neuronal nicotinic receptors has essentially the same properties as the above, except that it is formed from only two subunit types, α, and β. Here again, the structure is pentameric (α₂β₃ at least in the cases analyzed). There is evidence that the glycine receptor also has the pentameric structure, although forming an anion channel, and electron-optical studies have recently indicated a further pentameric structure for the GABA_A receptors.

The function of Membrane Receptors

Membrane receptors perform fast signaling since their transduction is independent of any intracellular or membrane-diffusible factor. In addition to the usual case of receptor activation by a presynaptically released transmitter, the transmitter molecule may arrive on the intracellular side. The latter subdivision includes those receptors where the signaling occurs across an organelle membrane {the ryanodine receptor and most of the inositol 1,4,5- trisphosphate [Ins(1,4,5)P3] receptors}, in which Ca²⁺ ions are transferred from an intracellular store in response to the binding of Ins(1,4,5)P3 or, for the ryanodine receptor, some other signal, perhaps Ca²⁺ itself.

Amino Acid-Gated Channels

Fast synaptic transmission in the central nervous system (CNS) is believed to be mediated mainly by amino acid neurotransmitters that activate ligand-gated ion channels. The major excitatory transmitter in the brain is thought to be L-glutamate whereas γ-aminobutyric acid (GABA) and glycine serve as the major inhibitory neurotransmitters in the brain and spinal cord, respectively. Activation of these receptors results in the rapid flux of ions through integral ion channels, which results in depolarization or hyperpolarization of the target neuron.

Fig.1 Structure of the rat GABA, receptor al subunit with deduced amino acid sequence mediating amino acid residues implicated in ligand-binding domains. (Smith, 1995)

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Reference

1. Smith, G. B., and Olsen, R. W. Functional domains of GABA_A receptors. Trends Pharmacol Sci. 1995, 16(5): 162-8.