Simpson / Fitch Applied Neurophysiology

With Particular Reference to Anaesthesia
1. Auflage 2013
ISBN: 978-1-4831-9348-9
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 366 Seiten

Applied Neurophysiology is intended to promote understanding of the structure and function of the human nervous system for anesthetists. For that reason this book presented concepts rather than critical discussions of experimental work. This book is organized into five parts. There are chapters intended for specialists such as those on vision, control of gaze, hearing and locomotion that were included in order to introduce concepts on brain stem automatisms and cortical function necessary to understand respiration and conscious awareness. There is also a chapter on autonomic nervous system which provides an account of the regulation of the cerebral circulation. The final sections of this volume also include quantitative data and references to original studies which were not thought necessary in other sections. This book will be of interest to anesthetists, clinicians, psychologists, speech pathologists and even neurologists in training.

Autoren/Hrsg.

Simpson, J. A.

Fitch, W.

Leseproben

Chapter 1 The excitable cell
Publisher Summary
This chapter discusses a special feature of the excitable cells—nerve and muscle—that is, the permeability that can be changed by processes that either increase or decrease the potential difference. Membrane permeability decreases during the outward flow of potassium current and increases with inward flow. Although the evidence is less satisfactory, it is likely that a similar voltage-dependent gate is opened at the internal end of the potassium channel. The node of Ranvier of the mammalian myelinated nerve fiber is believed to have many sodium but few potassium channels. The facility with which ions cross the membrane determines its electrical resistance. There is experimental evidence that glial cells are not necessary for production of action potentials by neurons, but it has been suggested that they act as a buffering mechanism to limit local concentrations of K+ outside nerve membranes producing action potentials, and at the same time, they accumulate potassium that would otherwise diffuse away from the nerve cell. The resting potential
Every living cell has a potential difference across its membrane due to the fact that charged particles are separated by a semi-permeable membrane which prevents the charged particles (ions) from redistributing themselves randomly. The special feature of the so-called ‘excitable cells’ (nerve, muscle) is that the permeability can be changed by processes which either increase (hyperpolarize) or decrease (depolarize) the potential difference. The membrane is a double layer of phospholipid molecules with specialized protein molecules inserted into it, some of which are structured to form channels which allow passage of water and ions (Fig. 1.1). There are at least two types of ion channels which differ in channel diameter, so restricting the ion species which each will pass (in fact the ion and its shell of water). Thus, one type allows ready passage of potassium and chloride ions. The other will pass, less readily, sodium ions and the similarly dimensioned lithium ions. The channels also have a selectivity filter for certain ion species, apparently because of energy barriers which remove the shell of water molecules around the ions. In the sodium channel the sodium ions bind to fixed negatively charged sites (probably oxygen atoms) which force them into single file. Similar constraints probably exist in the potassium channel. Thus the resting membrane has little permeability to ions. There are some molecules which are capable of inactivating the passage of ions by blocking the channels. Tetrodotoxin (from the puffer fish and other poisonous animals) is a complex molecule which can bind to the outward-facing molecule of the sodium channels and so block passage of sodium ions. Similarly, tetraethylammonium ion applied internally blocks potassium conductance.
Fig. 1.1 Schematic diagram of the outer membrane of an excitable cell (extracellular space above, cytoplasm below). The structural protein bounding layers are separated by a double layer of orientated lipids. The outer surface has a glycoprotein ‘backbone’ into which are set a ‘fuzz’ of polysaccharides, glycoproteins and glycolipids (right) with fixed anions. The membrane is leaky (upper) but a metabolically driven pump extrudes Na+ and introduces a smaller number of K+ ions into the cell. The difference in charge is seen as a resting potential across the membrane (positive outside with respect to the cytoplasm). This sets up a gradient of both potential and cation concentrations across the membrane. This is abolished and temporarily reversed when an electric current activates the opening gates of specific channels allowing Na+ ions to rush in and K+ to emerge more slowly. Calcium ions (Ca++) are necessary to open the gates. The sodium channel is soon closed by a voltage- and calcium-dependent inactivation gate but passive flux of K+ continues until the balance is restored. Specific channels for transfer of calcium are not shown in the diagram which illustrates three states — resting (upper), activated (middle) and inactivated (lower).
Beneath each channel and the Na–K–ATPase pump are illustrated the fluxes of Na+ and K+ due to each. Intracellular shifts are to the left of the dashed line, extracellular extrusions to the right. The net charge distribution across the membrane is shown bottom right. This illustrates the change from resting to action potential (depolarization) with after-hyperpolarization which is slowly abolished by the sodium pump. In addition to these specialized channels, there is an active pumping mechanism which transports sodium ions out of the cell and potassium ions into it. The structural basis for the pump is unknown but the action of certain poisons indicates that its carrier molecules are driven by energy derived from metabolic processes within the cell, probably from energy-rich ATP hydrolysed by Na-K-ATPase. The important part of this process is the removal of sodium from the cell cytoplasm as this permits the intracellular substance to have a sodium concentration only about 10 per cent of that of the extracellular fluid since the pump extrudes sodium at a rate that exactly balances the net passive inward membrane current. However, the membrane is slightly leaky to cations even when the channels are ‘closed’, although it is impermeable to anions other than Cl- (eg glutamic and aspartic ions) and the imbalance of positive charges produced by the pump sets up an electric potential across the membrane (the resting potential). Potassium ions, which pass more readily than sodium, are retained within the cell in higher concentration than in the external fluid and chloride ions are extruded until the combined electrochemical gradient for potassium and chloride ions is about zero, while the imbalance of sodium ions makes the interior of the cell at a negative potential relative to the exterior. The increased permeability to K+ ions on depolarizing the membrane is vastly greater than the opposite effect of a hyperpolarizing current. This phenomenon is termed delayed rectification. Muscle membrane has an additional anomalous rectification in the opposite direction. Membrane permeability decreases during the outward flow of potassium current and increases with inward flow. Depolarizing drugs cause sufficient loss of potassium from muscles to raise the level of plasma potassium. In patients with severe burns or with extensive injuries to soft tissues, administration of succinylcholine may raise the potassium efflux to levels which may cause cardiac arrest. There is a similar risk in its administration to patients with widespread denervation (polyneuritis) or myotonic dystrophy. The total body potassium is obviously significant for the excitable cell, but for its polarization and ability to produce action potentials, the external sodium level is more important than the level of potassium — a fact commonly overlooked in clinical medicine. Muscle is much more vulnerable than nerve to low potassium levels. Anomalous rectification seems to indicate a valve-like mechanism to resist a net outflow of potassium ions from the muscle cell, probably in the sarcoplasmic reticulum. So long as the sodium–potassium pump operates, the intracellular cytoplasm is rich in potassium and organic anions but poor in sodium and chloride compared to the external fluid. This is a potentially unstable situation with ion diffusion gradients across the membrane. If the metabolic pump fails, there is a slow but continuous inward movement of Na+ ions and compensatory loss of K+ ions so that both concentration gradients gradually disappear. This is a comparatively slow process as the permeability to sodium is so low. It takes many hours for the resting potential to drop significantly and during this time action potentials can still be generated. The electrochemical gradients are the motive force; but eventually the gradients are dissipated. This demonstrates the importance of the metabolic process for ‘re-charging the battery’, but also indicates that the ion shifts across the membrane are too slow to account for the action potential which is the hallmark of excitable cells, differentiating them from other cells which share the above mechanisms for polarizing the cell by electrochemical gradients. The action potential
The time courses of passive diffusion of ions into and out of the cell described so far are insufficient to account for the generation of an action potential. If the membrane of an excitable cell is depolarized beyond a critical level (by passing an electric current through it, or by increasing the extracellular concentration of potassium) it develops a high permeability to Na+ ions which then pass into the cell until the sodium equilibrium potential is reached. The influx of positive charges reverses the potential across the membrane. Activation of a sodium carrier has been postulated but it now seems that an adequate explanation is a voltage-regulated adjustment of a ‘gate’ mechanism at the external opening of the sodium channels (Fig. 1.2). At the normal resting potential, the channel appears to be occluded at its external opening by charged particles. When the membrane is depolarized (internal potential more positive) these gating particles are...