Ionotropic GABA

Johnston GA, Hanrahan JR, Chebib M, Duke RK, Mewett KN. 2006. Modulation of ionotropic GABA receptors by natural products of plant origin. Adv Pharmacol 54 285-316. 

Ionotropic GABA receptors (GABA(A)-Rs and GABA(C)-Rs) are inhibitory (hyperpolarizing) GABA-gated Cl channels that have sequence homology with nACh-Rs... 

Inhibitory glutamate receptors (iGlu-Rs) are inhibitory, Glu-gated ion channels related to the ionotropic GABA receptors and glycine receptors, the open channel being permeable to Cl- and sometimes to K+. The isoxazole alkaloid ibotenic acid activates iGlu-Rs (Table 3.3). 

Ozoe Y, Akamatsu M, Higata T, Ikeda I, Mochida K, Koike K, Ohmoto T, Nikaido T (1998) Picrodendrin and Related Terpenoid Antagonists Reveal Structural Differences Between Ionotropic GABA Receptors of Mammals and Insects. Bioorg Med Chem 6 481... 

Ju XL, Hao YL, Pei JF, Ozoe Y (2007) Investigation of Structural Requirements for Inhibitory Activity at the Rat and Housefly Picrotoxinin Binding Sites in Ionotropic GABA receptors using DISCOtech and CoMLA. Chemosphere 69 864... 

Nineteen different ionotropic GABA receptor subunits, named ai 6, P 3, 7i 3, S, e, 71 and d and 3, have been cloned from vertebrates. Experiments using recombinant expression and immunoprecipitation indicate that native vertebrate GABAa receptors contain at least a, fi and y subunits, sometimes also with <5, s, K ox 0 subunits, while GABAc receptors are believed to be composed only of p subunits. 

Ionotropic Those linked directly to ion channels such as those for Na+ (e.g. ACh nicotinic or some glutamate receptors) or Cl (GABA), involving fast events with increased membrane conductance and ion flux. 

GABAa receptor An ion channel (ionotropic) receptor for GABA. The GABAb receptor is a Gj protein-coupled receptor. 

Kerchner, G. A., Wang, G. D., Qiu, C. S., Huettner, J. E., and Zhuo, M. (2001) Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn an ionotropic mechanism. Neuron 32,477—488. 

Molecular Neuropharmacology Strategies and Methods is intended to bridge the gap between molecular biology and advanced chemistry. In addition, it attempts to include information about x-ray crystallographic analyses whenever available. This book discusses interdisciplinary interactions for monoamine transporters, amino acid transporters, ionotropic receptors, metabotropic glutamate receptors, GABA receptors, and other G protein-coupled receptors. 

There are two major types of receptor which are activated by neurotransmitters. These are the ionotropic and metabotropic receptors. The former receptor type is illustrated by the amino acid neurotransmitter receptors for glutamate, gamma-aminobutyric acid (GABA) and glycine, and the acetylcholine receptors of the nicotinic type. These are examples of fast transmitters in that they rapidly open and close the ionic channels in... 

Neurotransmitters can either excite or inhibit the activity of a cell with which they are in contact. When an excitatory transmitter such as acetylcholine, or an inhibitory transmitter such as GABA, is released from a nerve terminal it diffuses across the synaptic cleft to the postsynaptic membrane, where it activates the receptor site. Some receptors, such as the nicotinic receptor, are directly linked to sodium ion channels, so that when acetylcholine stimulates the nicotinic receptor, the ion channel opens to allow an exchange of sodium and potassium ions across the nerve membrane. Such receptors are called ionotropic receptors. 

Ionotropic receptors (bottom left) are ligand-gated ion channels. When they open as a result of the transmitter s influence, ions flow in due to the membrane potential (see p. 126). If the inflowing ions are cations (Na"", C, Ca ""), depolarization of the membrane occurs and an action potential is triggered on the surface of the postsynaptic cell. This is the way in which stimulatory transmitters work (e.g., acetylcholine and glutamate). By contrast, if anions flow in (mainly Cl ), the result is hyperpolarization of the postsynaptic membrane, which makes the production of a postsynaptic action potential more dif cult. The action of inhibitory transmitters such as glycine and GABA is based on this effect. 

Ionotropic receptors are ligand-gated ion channels (left half of the table). The receptors for stimulatory transmitters (indicated in the table by a ) mediate the inflow of cations (mainly Na""). When these open after binding of the transmitter, local depolarization of the postsynaptic membrane occurs. By contrast, inhibitory neurotransmitters (GABA and glycine) allow cr to flow in. This increases the membrane s negative resting potential and hinders the action of stimulatory transmitters hyperpolarization, 0). 

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