Inhibitory synapse

The amino acid glycine, a neurotransmitter at inhibitory synapses throughout the central nervous system (CNS),... 

B. Current Generated on Postsynaptic Membrane of Inhibitory Synapse following Stimulation with Gab... 

Gamma aminobutyric acid (GABA) receptors are located on the postsynaptic membranes of inhibitory synapses of both vertebrates and insects and contain within their membrane-spanning structure a chloride ion channel. They are found in both vertebrate brains and invertebrate cerebral ganglia (sometimes referred to as brains) as well as in insect muscles. Particular attention has been given to one form of this receptor—the GABA-A receptor—as a target for novel insecticides (Eldefrawi and Eldefrawi 1990). It is found both in insect muscle and vertebrate brain. The remainder of this description will be restricted to this form. 

Compare and contrast excitatory synapses and inhibitory synapses... 

At an inhibitory synapse, binding of the neurotransmitter to its receptor increases permeability of the membrane to K+ ions or to Ch ions through chemical messenger-gated channels. As a result, K+ ions may leave the cell down their concentration gradient carrying (+) charges outward or Cl ions... 

Altered release. Tetanus is an infectious disease caused by the bacterium Clostridium tetani. This bacterium produces a neurotoxin active on inhibitory synapses in the spinal cord. Motor neurons, which supply skeletal muscle and cause contraction, have cell bodies that lie in the spinal cord. Under normal circumstances, these motor neurons receive excitatory and inhibitory inputs from various sources. The balance of these inputs results in the appropriate degree of muscle tone or muscle contraction. Tetanus toxin prevents the release of gamma amino butyric acid (GABA), an important neurotransmitter active at these inhibitory synapses. Eliminating inhibitory inputs results in unchecked or unmodulated excitatory input to the motor neurons. The resulting uncontrolled muscle spasms initially occur in the muscles of the jaw, giving rise to the expression lockjaw. The muscle spasms eventually... 

Gray, E. G. Electron microscopy of excitatory and inhibitory synapses a brief review. Prog. Brain Res. 31 141,1969. 

As for the GABAa receptor, positive modulators that enhance glycine receptor activity have been identified. These include alcohols, neurosteroids, tropeines and the divalent metal ion Zn2+, which is highly enriched in some types of excitatory neuron [27], Zn2+ release from such neurons may potentiate glycine receptors at neighboring inhibitory synapses and thus facilitate inhibition following strong excitation. 

Laube, B., Maksay, G., Schemm, R. and Betz, H. Modulation of glycine receptor function a novel approach for therapeutic intervention at inhibitory synapses Trends Pharmacol. Sci. 23 519-527, 2002. 

Similar studies have been reported on the potentiation of inhibitory synapse formation by BDNF/TrkB. 

Physiological studies have identified both post- and presynaptic roles for ionotropic kainate receptors. Kainate receptors contribute to excitatory post-synaptic currents in many regions of the CNS including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are codistributed with AMPA and NMDA receptors, but there are also synapses where transmission is mediated exclusively by postsynaptic kainate receptors for example, in the retina at connections made by cones onto off bipolar cells. Extrasynaptically located postsynaptic kainate receptors are most likely activated by spill-over glutamate (Eder et al. 2003). Modulation of transmitter release by presynaptic kainate receptors can occur at both excitatory and inhibitory synapses. The depolarization of nerve terminals by current flow through ionotropic kainate receptors appears sufficient to account for most examples of presynaptic regulation however, a number of studies have provided evidence for metabotropic effects on transmitter release that can be initiated by activation of kainate receptors. The hyperexcitability evoked by locally applied kainate, which is quite effectively reduced by endocannabinoids, is probably mediated preferentially via an activation of postsynaptic kainate receptors (Marsicano et al. 2003). 

Interaction of excitatory and inhibitory synapses. On the left, a suprathreshold stimulus is given to an excitatory pathway (E) and an action potential is evoked. On the right, this same stimulus is given shortly after activating an inhibitory pathway (I), which results in an inhibitory postsynaptic potential (IPSP) that prevents the excitatory potential from reaching threshold. 

Drugs that modify this reflex arc may modulate excitatory or inhibitory synapses (see Chapter 21). Thus, to reduce the hyperactive stretch reflex, it is desirable to reduce the activity of the la fibers that excite the primary motoneuron or to enhance the activity of the inhibitory internuncial neurons. These structures are shown in greater detail in Figure 27-11. 

Alpha-2 CNS inhibitory synapses Presynaptic terminal at peripheral adrenergic synapses Gastrointestinal tract Pancreatic islet cells Decreased sympathetic discharge from CNS Decreased norepinephrine release Decreased motility and secretion Decreased insulin secretion... 

Short-Wave Cone Receptor ( ) Ganglion Cell — Inhibitory Synapse... 

Potier B, Dutar P, Lamour Y (1993) Different effects of omega-conotoxin GVIA at excitatory and inhibitory synapses in rat CA1 hippocampal neurons. Brain Res 616 236 11 Pragnell M, De Waard M, Mori Y, Tanabe T, Snutch TP, Campbell KP (1994) Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit. Nature 368 67-70... 

Harkany T, Holmgren C, Hartig W, Qureshi T, Chaudhry FA, Storm-Mathisen J, Dobszay MB, Berghuis P, Schulte G, Sousa KM, Fremeau RT, Jr., Edwards RH, Mackie K, Ernfors P, Zilberter Y (2004) Endocannabinoid-Independent Retrograde Signaling at Inhibitory Synapses in Layer 2/3 of Neocortex Involvement of Vesicular Glutamate Transporter 3. J Neurosci 24 4978 1988. 

Azdad K, Piet R, Poulain DA, Oliet SH (2003) Dopamine D4 receptor-mediated presynaptic inhibition of GABAergic transmission in the rat supraoptic nucleus. J Neurophysiol 90 559-65 Baimoukhametova DV, Hewitt SA, Sank CA, Bains JS (2004) Dopamine modulates use-dependent plasticity of inhibitory synapses. J Neurosci 24 5162-71 Bakker RA (2004) Histamine H3-receptor isoforms. Inflamm Res 53 509-16 Bakker RA, Lozada AF, van Marie A, Shenton FC, Drutel G, Karlstedt K, Hoffmann M, Lintunen M, Yamamoto Y, van Rijn RM, Chazot PL, Panula P, Leurs R (2006) Discovery of naturally occurring splice variants of the rat histamine H3 receptor that act as dominant-negative isoforms. Mol Pharmacol 69 1194-1206... 

Glutamate and GABA mediate transmission at most central excitatory and inhibitory synapses, respectively. Besides their quick actions at ionotropic receptors, glutamate and GABA, similarly to most other chemical mediators, can activate metabotropic receptors generally endowed with modulatory functions. 

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