Neuron membranes

Chapman GA, Moores K, Harrison D, Campbell CA, Stewart BR, Strijbos PJ (2000) Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J Neurosci 20 RC87... 

The liver is an organ that shows variable effects from trichloroethylene among species, and this can probably be attributed to interspecies differences in metabolism (see Section 2.4.2.1). Specifically, the apparent difference in susceptibility to trichloroethylene-induced hepatocellular carcinoma between humans and rodents may be due to metabolic differences (see Section 2.4.2.3). Kidney effects are also variable among species. Humans and mice are less sensitive than rats. In rats exposed chronically to trichloroethylene, toxic nephrosis characterized as cytomegaly has been reported (NTP 1988). The kidney effects in rats do not seem to be related to an increase in alpha-2 -globulin (Goldsworthy et al. 1988). Effects on the nervous system appear to be widespread among species, presumably due to interactions between trichloroethylene and neuronal membranes. 

Exactly how this transporter carries noradrenaline across the neuronal membrane is not known but one popular model proposes that it can exist in two interchangeable states. Binding of Na+ and noradrenaline to a domain on its extracellular surface could trigger a conformation change that results in the sequential opening of outer and inner channel gates on the transporter. This process enables the translocation of noradrenaline from the extracellular space towards the neuronal cytosol. 

The major inhibitory neurotransmitter in the cerebral cortex is y-aminobutyric acid (GABA). It attaches to neuronal membranes and opens chloride channels. When chloride flows into the neuron, it becomes hyperpolarized and less excitable. This mechanism is probably critical for shutting off seizure activity by controlling the excessive neuronal firing. Some antiepileptic drugs, primarily barbiturates and benzodiazepines, work by enhancing the action of GABA. 

Figure 1.1 The dopamine transporter terminates the action of released dopamine by transport back into the presynaptic neuron. Dopamine transport occurs with the binding of one molecule of dopamine, one chloride ion, and two sodium ions to the transporter the transporter then translocates from the outside of the neuronal membrane into the inside of the neuron.22 Cocaine appears to bind to the sodium ion binding site. This changes the conformation of the chloride ion binding site thus dopamine transport does not occur. This blockade of dopamine transport potentiates dopaminergic neurotransmission and may be the basis for the rewarding effects of cocaine.

Fromherz P, Dambacher KH, Ephardt H, Lambacher A, Muller CO, Neigl R, Schaden H, Schenk O, Vetter T (1991) Fluorescent dyes as probes of voltage transients in neuron membranes - progress report. Ber Bunsen-Ges Phys Chem 95(11) 1333—1345... 

Kuhn B, Fromherz P (2003) Anellated hemicyanine dyes in a neuron membrane Molecular Stark effect and optical voltage recording. J Phys Chem B 107(31) 7903—7913... 

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). 

G -protein-coupled receptors are often located on the presynaptic plasma membrane where they inhibit neurotransmitter release by reducing the opening of Ca2+ channels like inactivation and breakdown of the neurotransmitter by enzymes, this contributes to the neuron s ability to produce a sharply timed signal. An a2 receptor located on the presynaptic membrane of a noradrenaline-containing neuron is called an autoreceptor but, if located on any other type of presynaptic neuronal membrane (e.g., a 5-HT neuron), then it is referred to as a heteroreceptor (Langer, 1997). Autoreceptors are also located on the soma (cell body) and dendrites of the neuron for example, somatodendritic 5-HTia receptors reduce the electrical activity of 5-HT neurons. 

Figure 13.6. From left to right location of the P-amyloid region of amyloid precursor protein (APP) in relation to the neuronal membrane normal processing of APP inactivates P-amyloid abnormal processing of APP in Alzheimer s disease liberates intact P-amyloid.

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

Presynaptic receptor A receptor, either an autoreceptor or heteroreceptor, located on the presynaptic neuronal membrane which regulates the release of the neurotransmitter. 

FIGURE 5-14 Spatial buffering by astrocytes. This conceptual diagram indicates the pathways available for potassium ions to diffuse through the glial syncytium (light red) subsequent to their release from neuronal membranes (dark red) during neural activity. 

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