The transmission of nervous effects

On the surface of a resting living excitable cell such as muscle or nerve fibre there is a potential of the order of 100 mV., i.e. the outside is electropositive compared with the inside. Thus the surface of the intact unstimulated nerve is everywhere equi-potential (fig. 1 a). It may be worth while for a moment to try 

When a wave of excitation starts at a specified point on the fibre this potential difference is abolished and reversed and the surface becomes electronegative with regard to the unexcited portions of the fibre (fig. 16). ( Depolarization coincides with a change in the surface of the membrane of the cell which first allows Na ions from the tissue fluids to pass into the cell and K ions to pass outwards. In the undisturbed state, the cell membrane is relatively impermeable to the Na ions which are kept outside and the concentration of K ions inside the cell is greater than in the external fluids.) This induced negativity at the excited spot causes local electrical circuits to arise and so new paints of excitation are caused (Fig. Ic). The passage of electrical disturbance is shown in both directions. In the body, however, the fibres are stimulated at only one end, and hence induction is in one direction. 

This wave of excitation travels at about 120 m./sec. in the nerve of man at 37°. It should be noted that this value is much less than that of an electric current through a moist conductor. The temperature coefficient of the velocity of conduction in nerve is about 1-8 for a rise of 10°, and is of the same order as Hodgkin, Biol. Rev. 1951, 26, 379. 

We must now consider what happens when a nerve impulse reaches the end of a nerve fibre. The single nerve cell, together 

It should be noted that at a neuromuscular junction or at a ganglionic synapse there is a delay in the transmission of the excitatory process of about 2 msec. As stated above, the im- 

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Dale, Sir Henry (1953). A chemical phase in the transmission of nervous effects. Endeavour, AT, 117. 

By disrupting the biological function of the enzyme acetylcholinesterase, insecticides such as aldicarb, parathion and methamidophos (WHO la) prevent neurotransmitter molecules from being broken down, causing them to accumulate In the spaces between nerve cells. In this way acetyl-cholinesterase inhibitors effectively jam the transmission of nervous signals between nerve cells. 

Psychopharmaceuticals exert their intended effects in the central nervous system (CNS), where they primarily affect those processes that are involved in the transmission of informat ion between nerve cells. All these drugs act via one or several mechanisms that are thought to be impaired or functioning suboptimally in patients with mental disturbances. Such malfunctioning may... 

As with the mental effects of nicotine, the physiological effects are brought about by its actions on the nervous system, both peripheral and central. Nicotine changes the transmission of nerve impulses by binding to acetylcholine receptors, and induces the release of several chemical messengers, which in turn affect several body systems. 

The main action of physostigmine is on the parasympathetic nervous system. It is now known (52, 53) that physostigmine produces its effect by inhibition of the enzyme acetylcholinesterase. The role played by acetylcholinesterase in the transmission of nerve impulses at nerve endings (54, 55) and in the conduction of impulses along nerve and muscle fibers (56, 55) has been described in detail elsewhere. 

With cobra venom, the major effect is due to a toxin that acts on the nervous system. This neurotoxin is a small molecule, which can distribute throughout the body rapidly It acts like curare, paralysing the centre in the brain that controls breathing. By acting at the point where nerves control muscles it blocks the transmission of nerve impulses and causes muscle weakness and again affects breathing. The eyelids droop and speech becomes incoordinated. 

Although the exact biochemical mechanism of toxicity has not been identified for toluene, it is known that the primary toxic effect of toluene is dysfunction of the brain and central nervous system (CNS-nar-cosis). The main function of neurons is to conduct electrochemical signals to one, several, or thousands of other cells. The normal physiology of these neurons is, in turn, largely dependent on the integrity of the cell membrane, which polarizes and depolarizes during the transmission of these signals. Thus, the most probable mechanism of toxicity is the unique... 

Effects of cannabinoids on the sympathetic nervous system have been studied in isolated tissues and in pithed animals (Table 4). Sympathetic neurons were usually activated by electrical stimulation. Activation of CBi receptors led to inhibition of noradrenaline and/or ATP release and, consequently, to inhibition of the effector responses in the heart, in mesenteric and renal blood vessels and in the vas deferens. Figure 5A shows that cannabinoids inhibit sympathetic neuroeffector transmission in the heart. Sympathetically mediated vasoconstriction was inhibited in many tissues of pithed rats and rabbits. Sympathetic tone is depressed during long-term A -tetrahydrocannabinol administration in humans the presynaptic inhibitory effect of cannabinoids on sympathetic axon endings maybe the basis of this effect. 

Based on this type of reasoning, investigators have divided defensive substances into (1) the acute toxins (qualitative defenses) that are present in very low concentrations in plant tissues and which exert their effects on herbivores by interfering with some basic metabolic process such as transmission of nervous impulses, and (2) digestibility-reducing substances (quantitative defenses) that are present in higher concentrations in plant tissues, that act in the gut of the animal to reduce its ability to utilize its food, particularly proteins, and whose effectiveness increases directly with their concentration (Cates and Rhoades, 1977 Feeny, 1970, 1976 McKey, 1974 Rhoades and Cates, 1976). Qualitative defenses... 

CNS depressants. These are compounds which have the predominant effect of depressing or blocking the activity of the central nervous system, often by interfering with the transmission of information across synapses. An example of this type of agent is BZ. .. Cannabinols and phenothiazine type compounds are other potential incapacitating agents which seem to act basically as CNS depressants. The primary effects of these agents, however, are to sedate and destroy motivation rather than to disrupt the ability to think. 

That acetylcholine, isolated from vegetable material, had a strong physiological action in animals, was known early in the present century. That it might be the mammalian body s principal neurotransmitter was suspected by Otto Loewi (1921) working in Vienna. Yet the world of pharmacology was unprepared, and shaken, when, 5 years later, Loewi and Navratil (1926) showed that this was indeed the case. Most workers were surprised that transmission of nervous impulses across a synapse (gap) should be effected by a chemical, because so many believed it would be electrical. 

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