Ionotropic Receptors

The first class of receptors contains in their molecular complex an intrinsic ion channel. Receptors of this class include those for a number of amino acids, including glutamate (e.g., the NMDA [N-methyl-d-aspartate] receptor) and GABA ( '-aminobutyric acid via the GABAa receptor), as well as the nicotinic acetylcholine (ACh) receptor and the serotonin3 (5-HT3) receptor. Ion channels are integral membrane proteins that are directly responsible for the electrical activity of the nervous system by virtue of their regulation of the movement of ions across membranes. Receptors containing intrinsic ion channels have been called ionotropic and are generally composed of four or five subunits that open transiently when neurotransmitter binds, allowing ions to flow into (e.g., Na+, Ca2+, CI") or out of (e.g., K+) the neuron, thereby generating synaptic potential (see Figure 1-1).

Often, the ionotropic receptors can be composed of different compositions of the different subunits, thereby providing the system with considerable flexibility. For example, there is extensive research into the potential development of an anxiolytic that is devoid of sedative effects by targeting GABAa receptor subunits present in selected brain regions. In general, neurotransmission that is mediated by ionotropic receptors is very fast, with ion channels opening and closing within milliseconds, and regulates much of the tonic excitatory (e.g., glutamate-mediated) and inhibitory (e.g., GABA-mediated) activity in the CNS; as we discuss below, many of the classical neurotransmitters (e.g., monoamines) exert their effects on a slower time scale and are therefore often considered to be modulatory in their effects.

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