Nervous conduction, mechanism

The mode of action, which is now well authenticated and understood, involves the irreversible inhibition of the enzyme acetylcholinesterase, which is essential to nervous conduction in insects, by phosphorylation of a hydroxy group at the active site. The detailed mechanisms have been reviewed by O Brien (B-67MI10700, B-76MI10701). 

Again, the critical experiments which demonstrated the mechanisms of this process were performed by Hodgkin, by Keynes, and by A. F. Huxley. They used in their experiments the biggest nerve they could find - the giant axon of the squid, which is so wide, being up to a millimetre in diameter, that it is relatively easy to inject test substances down inside it and to study their effects. They first showed that nervous conduction is dependent on energy metabolism. Nerves poisoned with cyanide, which prevents oxida-... 

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

The clinical effects of chloroform toxicity on the central nervous system are well documented. However, the molecular mechanism of action is not well understood. It has been postulated that anesthetics induce their action at a cell-membrane level due to lipid solubility. The lipid-disordering effect of chloroform and other anesthetics on membrane lipids was increased by gangliosides (Harris and Groh 1985), which may explain why the outer leaflet of the lipid bilayer of neuronal membranes, which has a large ganglioside content, is unusually sensitive to anesthetic agents. Anesthetics may affect calcium-dependent potassium conductance in the central nervous system (Caldwell and Harris 1985). The blockage of potassium conductance by chloroform and other anesthetics resulted in depolarization of squid axon (Haydon et al. 1988). 

In summary, cardiac glycosides increase contractile force and reduce heart rate and AV conduction. In addition, cardiac glycosides suppress the sympathetic hyperactivity which occurs in advanced stages of congestive heart failure via a complex mechanism involving the central nervous system. 

LAs block nerve conduction when applied locally to nervous tissue by a voltage- and frequency-dependent inhibition of sodium currents (see Voltage-gated Sodium Channels Structure and Function1). Due to this mechanism, they preferentially block hyperexcitable cells and interfere comparatively less with normal physiological sensory and motor function. However, they are not selective for pain-relevant sodium channel subtypes so that they have a relatively high risk of adverse effects associated with the central nervous and cardiovascular systems when administered systemically. Known LAs are not active when administered orally. 

These results provide additional evidence that enzyme repression is an important mechanism in B(a)P-induced neurotoxicity and likely results from oxidative stress in the nervous system. Inhibition of Na /K -ATPase, an important enzyme in muscle contraction and nerve excitability, in addition to decreased motor conduction velocities may explain the suppression of motor activity observed in B(a)P intoxicated rats (Kim et al, 2000 Saunders et al, 2001). Furthermore, there is also strong experimental evidence showing that oxidative stress and lipid peroxidative products can cause decreases in dopamine and inhibit Na /K -ATPase activity as well (Madrigal et al, 2003). 

In contrast to the endocrine system that achieves long-term control via chemical (hormonal) mechanisms, the nervous system relies on more rapid mechanisms of chemical and electrical transmission to propagate signals and commands. The rapid conduction of impulses is essential in allowing the nervous system to mediate shortterm and near immediate communication and control between various body systems. 

In response to these activation stimuli, action potentials are conducted towards the central nervous system, where they may elicit reflex responses in respiratory pattern (e.g. rapid, shallow breathing), or alterations in pulmonary mechanics. As the action potentials, on their way to the central nervous system, pass the terminal ramifications of axon dendrites, antidromic conduction occurs and signals are propagated toward peripheral nerve... 

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