Axonal membranes

The axonal membrane is a lipid bilayer in the nerve fibre. Ionic channels and other proteins are located in the membrane to achieve electrical activity. Action potentials are generated and conducted along the membrane. 

The putative binding site for local anaesthetic molecules at the sodium channel has been identified as two amino acids in the sixth membrane-spanning segment of domain IV [2]. This binding site is located directly underneath the channel pore and can only be reached from the internal side of the membrane. Because local anaesthetics are applied exterior to the nerve fibre, they have to penetrate the axonal membrane before they can bind to the channel. 

Axon Reflex Axonal Guidance Axonal Membrane Azole... 

Pyrethroids, such as p,p -DDT, are toxic because they interact with Na+ channels of the axonal membrane, thereby disturbing the transmission of nerve action potential (Eldefrawi and Eldefrawi 1990, and Chapter 5, Section 5.2.4 of this book). In both cases, marked hydrophobicity leads to bioconcentration of the insecticides in the axonal membrane and reversible association with the Na+ channel. Consequently, both DDT and pyrethroids show negative temperature coefficients in arthropods increasing temperature brings decreasing toxicity because it favors desorption of insecticide from the site of action. 

Myelin facilitates conduction. Myelin is an electrical insulator, although its function of facilitating conduction in axons has no exact analogy in electrical circuitry [3], In unmyelinated fibers, impulse conduction is propagated by local circuits of ion current that flow into the active region of the axonal membrane, through the axon, and... 

CD9 is a well-characterized hematopoietic tetraspan protein that has been shown to be present in CNS and PNS myelin, although it is present at higher levels in PNS myelin. In other cells, it is involved in integrin signaling and cell adhesion and motility. It is expressed at late stages of myelination and in the CNS is primarily found in paranodal junctions [34]. While compact CNS myelin is apparently normal in CD9-null animals, the paranodal loops are often disconnected from axonal membranes, and the transverse bands of the paranodal loops are lost. In the PNS, in addition to altered paranodes, hypermy-elination occurs. Thus, this tetraspan protein appears to act primarily at paranodes, where it is crucial for normal paranodal junctions. 

Curiously, functions proposed for some brain KRPs [55] are very different from functions proposed for similar or identical KRPs in no-neuronal cells. For example, members of the kinesin-13 family have been implicated in both mitotic spindle function and in axonal membrane transport. Similarly, a mouse kinesin-4 was reported to associate with unidentified MBOs in neurites, but its chicken homolog bound to chromosomal DNA and mediates chromosome movements in the mitotic spindle. Finally, a kinesin-6 was originally found to have a role in mitotic spindle function, but members of the kinesin-6 family were also implicated in the transport of MTs into dendrites [56]. 

The charge on the inside of a cell is negative with respect to the surrounding solution. A potential difference of about —70 mV forms across the axon (cell membrane) when the cell is at rest , i.e. before passing an impulse - we sometimes call it a rest potential, which is caused ultimately by differences in concentration either side of the axon (membrane). 

Fundamentally, the eel is simply a living battery. The tips of its head and tail represent the poles of the eel s battery . As much as 80 per cent of its body is an electric organ, made up of many thousands of small platelets, which are alternately super-abundant in potassium or sodium ions, in a similar manner to the potentials formed across axon membranes in nerve cells (see p. 339). In effect, the voltage comprises thousands of concentration cells, each cell contributing a potential of about 160 mV. It is probable that the overall eel potential is augmented with junction potentials between the mini-cells. 

Synthesis of noradrenaline (norepinephrine) is shown in Figure 4.7. This follows the same route as synthesis of adrenaline (epinephrine) but terminates at noradrenaline (norepinephrine) because parasympathetic neurones lack the phenylethanolamine-N-methyl transferase required to form adrenaline (epinephrine). Acetylcholine is synthesized from acetyl-Co A and choline by the enzyme choline acetyltransferase (CAT). Choline is made available for this reaction by uptake, via specific high-affinity transporters, within the axonal membrane. Following their synthesis, noradrenaline (norepinephrine) or acetylcholine are stored within vesicles. Release from the vesicle occurs when the incoming nerve impulse causes an influx of calcium ions resulting in exocytosis of the neurotransmitter. 

The axonal transport of APP in neurons is mediated by the direct binding of APP to the kinesin light chain subunit of kinesin I. An axonal membrane compartment contains APP, P-secretase, and PSl, and the fast anterograde axonal transport of this compartment is mediated by APP and kinesin I. APP proteolysis in this... 

Polyneuritis is a disorder of the peripheral nerves. It involves damage to the myelin sheath. The condition is due to inflammation of the axonal membrane caused by viral or bacterial attack, i.e. an antoimmnne disease. Guillain-Barre syndrome is one form of polynenritis and is an example of an autoimmune disease caused by immune mimicry in response to a bacterial or viral antigen. It is discnssed in Chapter 17. 

The cytoskeleton is found near the axonal membrane and consists of microfilaments linked internally to microtubules and the plasma membrane by a network of filamentous protein that includes the brain-specific protein fodrin. This protein forms attachment sites for integral membrane proteins either by means of the neuronal cell adhesion molecule (N-CAM) or indirectly by means of a specific protein called ankyrin in the case of the sodium channels. This may provide a means whereby the sodium channels are concentrated in the region of the nodes of Ranvier. Thus the cortical cytoskeleton plays a vital role in neuronal function by acting as an attachment site for various receptors and ion channels, but also for s)maptic vesicles at nerve terminals, thereby providing a mechanism for concentrating the vesicles prior to the release of the neurotransmitter. 

Cuanethidine possesses high affinity for the axolemmal and vesicular amine transporters, it is stored instead of NE, but is unable to mimic the functions of the latter, in addition, it stabilizes the axonal membrane, thereby impeding the propagation of impulses into the sympathetic nerve terminals. Storage and release of epinephrine from the adrenal medulla are not affected, owing to the absence of a re-uptake process. The drug does not cross the blood-brain barrier. 

The activation a2-adrenoceptors is particularly important in the negative feedback control of adrenergic outflow, centrally in the vasomotor centers and peripherally at the presynaptic axonal membrane of adrenergic neurons. 

Studies suggest that the receptor for the local anesthetic is near the inner (axoplasmic) surface of the cell membrane, because quaternary analogues of local anesthetics are quite effective when applied to the inside of the axonal membrane but are inactive when placed on the outside of the membrane. These permanently charged molecules cannot penetrate to the receptor sites. 

The development of an action potential depends on a particular property of the axonal membrane,... 

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