Axonal smooth membranes

Palytoxin (PTX) is one of the most potent marine toxins known and the lethal dose (LD q) of the toxin in mice is 0.5 Mg/kg when injected i.v. The molecular structure of the toxin has been determined fully (1,2). PTX causes contractions in smooth muscle (i) and has a positive inotropic action in cardiac muscle (4-6). PTX also induces membrane depolarization in intestinal smooth (i), skeletal (4), and heart muscles (5-7), myelinated fibers (8), spinal cord (9), and squid axons (10). PTX has been demonstrated to cause NE release from adrenergic neurons (11,12). Biochemical studies have indicated that PTX causes a release of K from erythrocytes, which is followed by hemolysis (13-15). The PTX-induced release of K from erythrocytes is depress by ouabain and that the binding of ouabain to the membrane fragments is inhibited by PTX (15). 

The action potential is propagated by local spread of depolarization. How does the action potential propagate smoothly down an axon, bringing new channels into play ahead of it Any electrical depolarization or hyperpolarization of a cell membrane spreads a small distance in either direction from its source by a purely passive process often called cable or electrotonic spread. The spread occurs because the intracellular and extracellular media... 

Neurons possess a cell body (also referred to as a soma or perikaryon), which consists of a nucleus surrounded by cytoplasm and membrane. The survival of the rest of the neuron is dependent upon the integrity of the cell body. Axons and dendrites are both processes that extend from the cell body. Also located in the cell body are the Golgi apparatus, smooth ER, rough ER, and mitochondria. Cytoskeletal elements—microtubules and neurofilaments—are also present. 

The cytoplasmic channels or paranodal loops at the lateral end of the internode are a major site of myelin-axon adhesion. The membrane of the inner or adaxonal surface of the myelin sheath is in direct contact with the axons. Their cytoplasmic channels may transmit axonal signals that regulate myelin formation and help determine the length and thickness of the myelin internode. These channels contain microtubules and other cytoskeletal components for transport and stability and mitochondria for energy. Also, in some areas, they contain smooth endoplasmic reticulum and free polysomes for the synthesis of local membrane components. In addition, membranes of noncompact myelin serve special functions that are reflected by unique molecular composition. 

Typically, the presynaptic ending is further distinguished from the postsynaptic component by the conspicuous presence of neurotransmitter-filled vesicles. In response to presynaptic membrane depolarization, the vesicles exocytose their contents into the cleft through complicated membrane-trafficking events. The presynaptic axon terminal (bouton) of the presynaptic component also contains other organelles such as mitochondria, smooth endoplasmic reticulum, microtubules, and neurofilaments. The presynaptic membrane is variably populated by docking/fusion apparatus, ion channels, and other protein constituents. The 20-30 nM wide synaptic cleft separates the pre- and postsynaptic membranes and generally contains a dense plaque of intercellular material that includes microfilaments. 

The ultrastructure of NA fibers of the cerebellar cortex and other parts of the rat CNS was analyzed with pre-embedding dopamine-y5-hydroxylase immunohistochemistry by Olschowka et al. (1981). Immunoreaction product was present in the axoplasm, associated with smooth endoplasmatic reticulum, Golgi apparatus, synaptic and large dense core vesicles and the outer membranes of mitochondria. Large varicosities were interconnected by narrow intervaricose axon segments. Varicosities, filled with clear, round synaptic vesicles and large dark-core vesicles, made asymmetric contacts with dendrites, but never with somata or axons. More than 50% of the labelled varicosities in the cerebellum made synaptic contacts most of them with dendritic shafts, fewer on spines. 

The smooth flexible surface of the erythrocyte plasma membrane allows the cell to squeeze through narrow blood capillaries. Some cells have a long, slender extension of the plasma membrane, called a cilium or flagellum, which beats in a whiplike manner. This motion causes fluid to flow across the surface of an epithelium or a sperm cell to swim through the medium. The axons of many neurons are encased by multiple layers of modified plasma membrane called the myelin sheath. This membranous structure is elaborated by... 

FIGURE 5-3 Variation in biomembranes in different cell types, (a) A smooth, flexible membrane covers the surface of the discoid erythrocyte cell, (b) Tufts of cilia (Cl) project from the ependymal cells that line the brain ventricles, (c) Many nerve axons are enveloped in a myelin sheath composed of multiple layers of modified plasma membrane. The individual myelin layers can be seen in this electron micrograph of a cross section of an axon (AX). The myelin sheath is formed by an adjacent supportive (glial) cell (SC). [Parts (a) and (b) from R. G. Kessel and R. H. Kardon, 1979, Tissues and Organs A Text-Atlas oT Scanning Electron Microscopy, W. H. Freeman and Company. Part (c) from P C. Cross and K. L. Mercer, 1993, Cell and Tissue Ultrastructure A Functional Perspective, W. FI. Freeman and Company, p. 137]... 

Lidocaine, like other local anesthetics, binds axonal membrane voltage-gated fast Na channels and thus prevents Na+ transport across the channels, thus inhibiting cell membrane depolarization. It is by this same mechanism that lidocaine exerts its effect as a class Ib antiarrhythmic to inhibit cardiac smooth muscle excitability and as an anti-epileptic drug to inhibit cortical excitability. Its lipophilic aromatic group allows the molecule to penetrate the nerve membrane, while its hydrophilic charged amine group is the portion of the molecule that actually binds the Na chaimel [1-3]. 

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