Nerve Axon flow

The excitable membrane of nerve axons, like the membrane of cardiac muscle (see Chapter 14) and neuronal cell bodies (see Chapter 21), maintains a resting transmembrane potential of -90 to -60 mV. During excitation, the sodium channels open, and a fast inward sodium current quickly depolarizes the membrane toward the sodium equilibrium potential (+40 mV). As a result of this depolarization process, the sodium channels close (inactivate) and potassium channels open. The outward flow of potassium repolarizes the membrane toward the potassium equilibrium potential (about -95 mV) repolarization returns the sodium channels to the rested state with a characteristic recovery time that determines the refractory period. The transmembrane ionic gradients are maintained by the sodium pump. These ionic fluxes are similar to, but simpler than, those in heart muscle, and local anesthetics have similar effects in both tissues. 

A primary lipidosis has been described in human optic nerves affected by amiodarone. One study has shown that intracytoplasmic inclusions may mechanically or biochemically block axoplasmic flow in large optic nerve axons, resulting in optic disc edema and hemorrhage. 

Hohmann AG, Herkenham M (1999a) Cannabinoid receptors undergo axonal flow in sensory nerves. Neuroscience 92 1171-1175... 

Acetylcholinesterase comes into play in the following way. The arrival of a nerve impulse at the end plate of the nerve axon causes an influx of Ca +. This causes the acetylchoUne-containing vesicles to migrate to the nerve cell membrane that is in contact with the muscle cell. This is called the presynaptic membrane. The vesicles fuse with the presynaptic membrane and release the neurotransmitter. The acetylcholine then diffuses across the nerve synapse (the space between the nerve and muscle cells) and binds to the acetylcholine receptor protein in the postsynaptic membrane of the muscle cell. This receptor then opens pores in the membrane through which Na and K+ ions flow into and out of the cell, respectively. This generates the nerve impulse and causes the muscle to contract. If acetylcholine remains at the neuromuscular junction, it will continue to stimulate the muscle contraction. To stop this continued stimulation, acetylcholine is hydrolyzed, and hence, destroyed by acetylcholinesterase. When this happens, choline is no longer able to bind to the acetylcholine receptor and nerve stimulation ceases. 

Molecular dynamics of biological function must be done in nonequilibrium conditions where flows occur, because almost all biology occurs in these conditions. Simulations have difficulty in dealing with the action potentials of nerve and muscle fibers. Molecular dynamics cannot compute the biUions of trajectories of ions that cross membranes to make action potentials, lasting milhseconds to nearly a second, flowing centimeters to meters down nerve axons. Simulations at present cannot deal with flows that are controlled by channels on the atomic scale but couple to boundary conditions on the macroscopic scale, milUmeters away from the channel. Many biological systems use atomic scale structures this way to control macroscopic function. 

The use of labeled cholesterol or its precursor, mevalonate, has the appeal that a limited number of products are presumably formed and that the lipid is believed to turn over very slowly within the nervous system. It should be noted, however, that the observed slow cholesterol turnover reflects primarily the major brain pool of this lipid, myelin. Axonal flow studies are however directed at neurons, not at the glial cells that synthesize myelin. MacGregor et al., (1973) noted that following injection of cholesterol into the lumbar region of the chick, aproximodistal gradient of cholesterol was found in the sciatic nerve. The rate was thought to be about that observed for protein. Both cholesterol and cholesterol ester were detected, but the relative proportions were variable. A slow and fast rate of axonal flow were... 

Coenzyme A is synthesized in the mitochondria. ChAc is probably synthesized in the body of the nerve cell and is thought to be transported down the axon towards the nerve endings with the axonal flow of cytoplasm. The nerve endings are richer in ChAc than any other part of the neuron, but the exact localization of the enzyme in the nerve endings is not yet certain it may be present in the synaptic vesicles and/or in the cytoplasm of the nerve endings. 

The idea that signals are transmitted along the nerve channels as an electric current had arisen as early as the middle of the nineteenth century. Yet even the first measurements performed by H. Helmholtz showed that the transmission speed is about lOm/s (i.e., much slower than electric current flow in conductors). It is known today that the propagation of nerve impulses along the axons of nerve cells (which in humans are as long as 1.5m) is associated with an excitation of the axon s outer membrane. 

Saltatory conduction results in a significant increase in the velocity of conduction of the nerve impulse down the axon compared to that of local current flow in an unmyelinated axon (see Table 4.2). The speed of conduction is... 

Once an electrical impulse invades the presynaptic axon terminal, it causes the release of chemical neurotransmitter stored there (Fig. 1—3). Electrical impulses open ion channels, such as voltage-gated calcium channels and voltage-gated sodium channels, by changing the ionic charge across neuronal membranes. As calcium flows into the presynaptic nerve, it anchors the synaptic vesicles to the inner membrane of the nerve terminal so that they can spill their chemical contents into the synapse. The way is paved for chemical communication by previous synthesis and storage of neurotransmitter in the first neuron s presynaptic axon terminal. 

When a local anesthetic is injected near a nerve, it blocks the flow of electrons along the axons and eliminates the pain without loss of consciousness. These effects are reversible. When administering a local anesthetic, one must remember that the larger the diameter of the nerve fiber, the more anesthetic is needed to produce anesthesia. 

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