Postsynaptic neuronal membrane

When the action potential reaches the synaptic bouton, depolarisation triggers the opening of voltage-operated calcium channels in the membrane (Figure 2.5). The concentration gradient for Ca2+ favours the passive movement of this ion into the neuron. The subsequent rise in cytoplasmic Ca2+ ion concentration stimulates the release of neurotransmitter into the synaptic cleft, which diffuses across this narrow gap and binds to receptors located on the postsynaptic neuronal membrane (Figure 2.5). 

Postsynaptic receptor A receptor located on the postsynaptic neuronal membrane mediating the physiological effects of the neurotransmitter. 

The basis for the antihypertensive activity of the ganglionic blockers lies in their ability to block transmission through autonomic ganglia (Fig. 20.2C). This action, which results in a decrease in the number of impulses passing down the postganglionic sympathetic (and parasympathetic) nerves, decreases vascular tone, cardiac output, and blood pressure. These drugs prevent the interaction of acetylcholine (the transmitter of the preganglionic autonomic nerves) with the nicotinic receptors on postsynaptic neuronal membranes of both the sympathetic and parasympathetic nervous systems. 

Ammonia also has deleterious effects on excitatory neurotransmission (Szerb and Butterworth, 1992, review) where effects on both presynaptic and postsynaptic neuronal membranes have been reported. NH + ions, in pathophysiologically relevant concentrations, interfere with excitatory neurotransmission by preventing the action of glutamate at the postsynaptic receptor. In addition, NH depolarizes neurons to a variable degree without consistently changing membrane resistance, probably by reducing K concentrations. 

Known as "free radical synthesis," It enables the organophosphate to bind to postsynaptic neuronal membranes... 

FIGURE 5.5 A simple model of synaptic transmission. The pres)fnaptic neuronal membrane (green) releases the netirotransmitter (triangles) in the synaptic deft. The neurotransmitter travels through the synapse and eventually binds to a receptor (blue) expressed by the postsynaptic neuronal membrane. If the neurotransmifter is soluble in water, it will bind to a surface-accessible region of its receptor. The postsynaptic membrane is represented with a lipid bUayer (cholesterol in red, phospholipids in green). 

Neurons do not touch each other a gap called a synapse or synaptic cleft separates the axon of one neuron and the dendrites of the next neuron. All the signals must cross the synapse to continue on its path through the nervous system. In the brain, the nervous impulse is carried across synapses by electrical conduction, while in other parts of the body impulses are carried across synapses by an electrochemical process. When an impulse comes, the membrane at the end of the axon depolarizes, opening the gated ion chaimels, and calcium ions are allowed to enter the cell. The presence of calcium ions determines the release into the synapse of a chemical species called neurotransmitter which moves across the synapse and binds to specific receptors (different proteins serve as receptors for different neurotransmitters) on the postsynaptic neuron membrane that is about to receive the impulse. 

Figure 5.1 Mechanism of action at a chemical synapse. The arrival of an action potential at the axon terminal causes voltage-gated Ca++ channels to open. The resulting increase in concentration of Ca++ ions in the intracellular fluid facilitates exocytosis of the neurotransmitter into the synaptic cleft. Binding of the neurotransmitter to its specific receptor on the postsynaptic neuron alters the permeability of the membrane to one or more ions, thus causing a change in the membrane potential and generation of a graded potential in this neuron.

Na+ channels to depolarize the membrane all the way to threshold however, it brings the membrane potential closer toward it. This increases the likelihood that subsequent stimuli will continue depolarization to threshold and that an action potential will be generated by the postsynaptic neuron. 

Temporal summation occurs when multiple EPSPs (or IPSPs) produced by a single presynaptic neuron in close sequence exert their effect on membrane potential of the postsynaptic neuron. For example, an action potential in the presynaptic neuron produces an EPSP and partial depolarization of the postsynaptic neuron (see Figure 5.2). While the postsynaptic neuron is still depolarized, a second action potential in the presynaptic neuron produces another EPSP in the postsynaptic neuron that adds to the first and further depolarizes this neuron. 

Figure 5.3 Spatial summation. Multiple excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) produced by many presynaptic neurons simultaneously may add together to alter the membrane potential of the postsynaptic neuron. Sufficient excitatory input (A and B) will depolarize the membrane to threshold and generate an action potential. The simultaneous arrival of excitatory and inhibitory inputs (A and C) may cancel each other out so that the membrane potential does not change.

As a rule, oxygen radical overproduction in mitochondria is accompanied by peroxidation of mitochondrial lipids, glutathione depletion, and an increase in other parameters of oxidative stress. Thus, the enhancement of superoxide production in bovine heart submitochondrial particles by antimycin resulted in a decrease in the activity of cytochrome c oxidase through the peroxidation of cardiolipin [45]. Iron overload also induced lipid peroxidation and a decrease in mitochondrial membrane potential in rat liver mitochondria [46]. Sensi et al. [47] demonstrated that zinc influx induced mitochondrial superoxide production in postsynaptic neurons. 

Suppose that a specific neurotransmitter arrives at its ligand-gated ion channel, say a sodium ion channel. It will open and sodium ions will flow into the postsynaptic neuron, depolarizing its membrane. If this depolarization exceeds the threshold level, this will open voltage-gated sodium and potassium ion channels, generating an action potential that will flow down the dendrite to the cell body, and so on. 

Information transfer between two nerves in the brain occurs at synaptic junctions, across which chemical messengers (neurotransmitters) diffuse. The neurotransmitter binds to a receptor on the postsynaptic neurone, changing its membrane potential. If the membrane potential decreases, this either initiates an action potential or increases the likelihood that a further depolarisation, from stimulation by another nerve, will initiate an action potential. Such a neurotransmitter is described as excitatory. In contrast, if it increases the membrane potential, it reduces the likelihood of initiation of an action potential, such a... 

After release by exocytosis, the neurotransmitter diffuses across the cleft and binds to a receptor on the membrane of the postsynaptic neurone. The binding affects an ion channel, which changes the polarisation of the postsynaptic membrane (see below). 

Figure 14.11 Effects of excitatory and inhibitory neurotransmitters on initiation of an action potential in response to a second neurotransmitter. If the neurotransmitter released from the presynaptic membrane is inhibitory, it will reduce the likelihood that the second neurotransmitter will initiate an action potential. If the neurotransmitter is excitatory, it will increase the likelihood that the second neurotransmitter will initiate an action potential in the postsynaptic neurone. The second neurotransmitter arises from synapses of other axons.

Mechanism of Action A selective serotonin reuptake inhibitor that blocks the uptake of the neurotransmitter serotonin at CNS presynaptic neuronal membranes, increasing its availability at postsynaptic receptor sites. Therapeutic Effect Relieves depression. 

Mechanism of Action A tetracyclic compound that blocks reuptake norepi nephri ne by CNS presynaptic neuronal membranes, increasing availability at postsynaptic neuronal receptor sites, and enhances synaptic activity. Therapeutic Effect Produces antidepressant effect, with prominent sedative effects and low anticholinergic activity. Pharmacokinetics Slowly and completely absorbed after PO administration. Protein binding 88%. Metabolized in liver by hydroxylation and oxidative modification. Excreted in urine. Unknown if removed by hemodialysis. Half-life 27-58 hr. 

The GABAA receptor is now believed to be the major target site for anaesthetic action. The GABAA receptors exist as a family of subtypes with their pharmacology determined by their composition. GABAA receptors are pentameric and comprise of two a, two 3 (or 0), and one y (or s) subunits, which assemble to form a chloride-sensitive pore. When the receptor is activated, transmembrane chloride conductance increases, resulting in hyperpolarisation of the postsynaptic cell membrane and functional inhibition of the postsynaptic neurone. 

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