Axonal conduction

Na+ channels Cocaine is an antagonist of voltage-gated Na-i- channels, reducing axonal conduction and acting as a local anesthetic. This effect will be discussed at greater length in chapter 8. Cocaine s blockade of Na-i- channels as a contribution to its psychotropic effects is possible but has not been examined. 

Axonal conduction of action potentials was unaffected but the postsyntaptic potential of flight muscle fibers was prolonged. Central nervous system functions were affected but its exact mode of action remains unknown (2). 

Inhibition of norepinephrine release is probably caused by guanethidine s local anesthetic properties on sympathetic nerve terminals. Although the drug does not impair axonal conduction in sympathetic fibers, local blockade of membrane electrical activity may occur in nerve endings because the nerve endings specifically take up and concentrate the drug. 

Neural activity, which involves transmembrane ion fluxes and the release and uptake of chemical transmitters at synapses, is a highly important membrane-based function and a primary site of thermal perturbation in animals. Both axonal conduction and, especially, synaptic transmission may be involved in setting thermal tolerance limits. 

Several classes of insecticides are axonic poisons, which interfere with axonal conduction. Therefore, a brief account of axonal conduction will first be given. 

Figure 20.2. Proposed patliogenesis in acute motor axonal neuropatliy (AM AN) In AM AN tliere is primaiy axonal injury witliout T-cell inflammation and demyelination. Deposition of autoantibodies and complement on tlie axolemma is followed by sti uctural axonal injui y or alteration of axon conduction. Macrophages witliin die periaxonal space contribute to die axonal damage (B B-cell MO Macrophage, C5b-9 complement factors).

J, axonal conduction by preventing Na+ influx through fast Na channels—carba-mazepine, phenytoin also, at high doses, barbiturates and valproic acid... 

Condrea, E. and Rosenberg, P. (1968) Demonstration of phospholipid splitting as a factor responsible for increased permeability and block of axonal conduction induced by snake venom. II. Study on squid axons. Biochim. biophys. Acta (Amst.), 150,271-284. 

Rosenburgh, P. and Condrea, E. (1968) Maintenance of axonal conduction and membrane permeability in the presence of extensive phospholipid splitting. Biochem. Pharmacol., 17, 2033-2044. 

The protein theory is currently considered more likely to explain the process of anaesthesia, because general anaesthetics affect synaptic transmission rather than axonal conduction. Both the release of transmitter and the response of the postsynaptic receptors are affected. 

The nerve cell, or neuron, is an unusual looking cell (Fig. 8-1). A neuron may be only 0.1 mm in diameter but, may reach lengths of a meter or more. The threadlike extension from the cell body is the nerve fiber. These fibers interconnect in various special areas of the body, including the brain, the spinal cord, and the peripheral nerves. The function of the neuron is to transmit signals, or impulses. The dendrites specialize in receiving excitations, which may be from environmental stimuli (i.e., from peripheral parts of the body, or from another cell). The axon conducts the excitation away from the dendrite area (e.g., to the brain).1 This excitation, or impulse transmission, may be on a subconscious level. Transmissions of which the subject is not consciously aware are the type that control various body functions such as temperature, respiration, blood pressure, and peristaltic movements of the gastrointestinal tract. In addition to the traditional functions of a cell membrane, the membrane of the nerve fiber (the axon) has the role of transmitting the electrochemical impulses that are received from the dendrites. The additional protective device called the myelin sheath basically serves as an electrical insulator. 

The most fundamental studies on their mode of action have been those of Narahashi who worked with giant fibre preparations. He proposed that pyrethroids modify axonal conduction within the central nervous system of insects by altering the permeability of the nerve membrane to sodium and potassium ions (Narahashi, 1965 1974 1976 Burt and Goodchild, 1977 Clements and May, 1977). 

In vitn exposure to pyridostigmine causes the same ultrastructural changes as described in vivo experiments, such as swelling of subjunctional mitochondria and disorganization of contractile proteins. These alterations are accompanied by continuous fasciculations, Tetrodotoxin, an inhibitor of axonal conduction, which does not affect the NMJ but prevents development of fasciculations and alterations in pre- and postjunctional morphology by blocking axonal conduction (Adler etctl, 1992). 

Force development in skeletal muscle is achieved through the orderly recruitment of motor units. According to Henneman et al. s (1965) size principle, smaller motoneurons with smaller axons and slower conduction velocities have lower membrane capacitance, higher input resistance and lower rheobase, and thus are recruited first for a given synaptic input. For example, phrenic motoneurons with slower axonal conduction velocities are recruited first during inspiratory efforts, and type S and FR motor units are recruited first and more often, whereas type FInt and FF motor units are recruited later and less infrequently (Burke, 1981 Sieck and Fournier, 1989). 

Jan JT, Griffin DE. Induction of apoptosis by Sindbis virus occurs at cell entry and does not require virus replication. Journal of Virology 1999 73(12) 10296-10302 Kapoor R, Davies M, Smith KJ. Temporary axonal conduction block and axonal loss in inflammatory neurological disease. A potential role for nitric oxide Annals of the New York Academy of Sciences 1999 893 304—308... 

Redford EJ, Kapoor R, Smith KJ. Nitric oxide donors reversibly block axonal conduction demy-elinated axons are especially susceptible. Brain a journal of neurology 1997 120 (Pt 12) 2149-2157... 

Imaizumi, T., Lankford, K.L., Waxman, S.G., Greer, C.A., and Kocsis, J.D., Transplanted olfactory ensheathing cells remyelinate and enhance axonal conduction in the demyelinated dorsal columns of the rat spinal cord, /. Neurosci. 18, 6176-6185,1998. 

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