Distribution of ions in nerve and muscle

With the advent of flame photometry and other microanalytical techniques there is no difficulty in determining the quantities of ions present in a small sample of tissue. In order to arrive at the true intracellular concentrations, it is necessary to make corrections for the contents of the extracellular space, which may be done after measuring its size with the aid of a substance like Distribution of ions in nerve and muscle 29 Fig. 3.4. Electron micrograph of a freeze fracture preparation of...

The sodium gating current

An essential avenue towards a detailed understanding of the mode of operation of voltage-gated ion channels is to investigate the kinetics of the macroscopic ion currents in the manner adopted in the classical paper of Hodgkin & Huxley (1952). However, such studies are in one respect limited in their scope, because they throw light only on the kinetics of the open state, and reveal relatively little about the series of closed states through which the system must certainly pass during...

The sliding filament theory

Prior to 1954, most suggestions as to the mechanism of muscular contraction involved the coiling and contraction of long protein molecules, rather like the shortening of a helical spring. In that year the sliding filament theory was independently formulated by H. E. Huxley and Jean Hanson (using phase-contrast microscopy of myofibrils from glycerol-extracted muscles) and by A. F. Huxley and R. Niedergerke (using interference microscopy of living muscle fibres). In each case the authors showed...

The primary structure of voltagegated ion channels

The substantial voltages generated by the electric organ of the electric eel depend on the additive discharge of a large number of cells that are derived embryonically from muscle (see Fig. 2.4g). Their electrical excitability involves an increase of sodium permeability in the usual way, and this type of electric organ therefore provided ideal material first for isolating and purifying the sodium channel protein, and then for enabling its amino acid sequence to be determined. The initial...

The screwhelical mechanism of voltagegating

It is clear from the structural studies that every voltage-gated ion channel incorporates four S4 voltage-sensors that operate in parallel, there being as shown in Fig. 5.2 an identical one in each domain of the tetrameric potassium channels. In the monomeric sodium channels there are four sensors that vary Fig. 5.3. Superimposed family of sodium gating currents recorded from a squid axon dialysed with 350 mM TMAF (tetramethylammonium fluoride) and bathed in an artificial sea water with the...

The energy source

So far we have concentrated on the output side of the energy balance equation. It is now time to consider the question, what chemical changes supply the energy for muscular contraction 3 mois ADP -> ATP per glucose unit 3 mois ADP -> ATP per glucose unit Fig. 9.14. An outline of the breakdown of glycogen with the release of energy (in the form of ATP) in respiration. Energy for all bodily activities is ultimately derived from the food. Food energy is transported to the muscle as glucose or...

Excitation

Local Circuit Theory

Before considering the ionic basis of the mechanism of conduction of the nervous impulse, it is best to describe some facts concerning the process of Fig. 2.7. Diagrams illustrating the local circuit theory. The upper sketch represents a non-myelinated nerve fibre, the lower sketch a myelinated fibre. From Hodgkin (1958). Fig. 2.7. Diagrams illustrating the local circuit theory. The upper sketch represents a non-myelinated nerve fibre, the lower sketch a myelinated fibre. From Hodgkin (1958)....

Voltageclamp experiments

The increase in the sodium permeability of the membrane during the spike that is predicted by the sodium hypothesis can be measured with radioactive tracers by the method illustrated in Fig. 4.4. But although this approach has the advantage of specificity, in that it provides unambiguous information about sodium movements and not those of any other ion, the time resolution of tracer experiments is rather poor, and the results refer only to the cumulative effect of a large number of impulses. In...

The molecular structure of the acetylcholine receptor

The electric organs of the electric ray Torpedo provide a rich source of acetyl-choline receptors. They can be isolated by using their specific binding to the snake venom a-bungarotoxin. The receptors are pentameric proteins with a total molecular weight of about 290 kDa. The subunits are called the a, ff, y and 8 chains there are two a chains in each receptor and one of each of the others. The binding sites for acetylcholine are located on the a chains. The acetylcholine receptor was the first...

The structure of the myofibril

Each muscle fibre contains a large number of thin longitudinal elements called myofibrils. They have characteristic banding patterns, and the bands on adjacent myofibrils are transversely aligned so that the whole fibre appears striated. In order to see the striations by light microscopy it is necessary to fix and stain the fibres, or to use phase-contrast, polarized light or interference microscopy. Fig. 10.7 shows the striation pattern as seen by these methods and by low-power electron...

Inhibition in motoneurons

If the contraction of a particular limb muscle is to be effective in producing movement, it is essential that the muscles which oppose this action (the antagonists) should be relaxed. In the monosynaptic stretch reflex this is brought about by inhibition of the motoneurons of the antagonistic muscles. Fig. 8.4 shows the arrangement of the neurons involved. We have seen that group Ia fibres from the stretch receptors in a particular muscle synapse with motoneurons innervating that muscle. They...

Internal membrane systems

The next question to arise is, how does excitation at the cell surface cause release of calcium ions inside the fibre The first step in the solution of this problem was the demonstration by A. F. Huxley and R. E. Taylor that there is a specific inward-conducting mechanism located at the Z line in frog sartorius muscles. (We shall examine the striation pattern in detail later. But here it is worth noting that the markedly birefringent A bands alternate with the less birefringent I bands, and...

Structure of the cell membrane

All living cells are surrounded by a plasma membrane composed of lipids and proteins, whose main function is to control the passage of substances into and out of the cell. In general, the role of the lipids is to furnish a continuous matrix that is impermeable even to the smallest ions, in which proteins are embedded to provide selective pathways for the transport of ions and organic molecules both down and against the prevailing gradients of chemical activity. The ease with which a molecule...

Nerve and Muscle

Nerve and Muscle is an introductory textbook for students taking university courses in physiology, cell biology or preclinical medicine. Previous editions were highly acclaimed as a readable and concise account of how nerves and muscles work. The book begins with a discussion of the nature of nerve impulses. These electrical events can be understood in terms of the flow of ions through molecular channels in the nerve cell membrane. Then the view changes to consideration of synaptic transmission...

Slow synaptic potentials

Als Repetitive Stimulation

Dale used pharmacological criteria to distinguish two types of response to acetylcholine in peripheral tissues. Nicotinic responses are mimicked by nicotine and blocked by curare, whereas muscarinic responses are mimicked by muscarine and blocked by atropine. Correspondingly, we find there are two Fig. 8.7. Presynaptic inhibition. a (i) shows the EPSP produced in a motoneuron in response to stimulation (at time E) of the group Ia fibres innervating it. When a suitable inhibitory nerve is...

Myelinated nerve fibres

Nerve Fibre Diagram

In the myelinated nerve fibres of vertebrates, the excitable membrane is insulated electrically by the presence of the myelin sheath everywhere except at the node of Ranvier (Figs. 1.5,1.6,1.7). In the case of peripheral nerves, each stretch of myelin is laid down by a Schwann cell that repeatedly envelops the axis cylinder with many concentric layers of cell membrane (Fig. 1.7) in the central nervous system, it is the cells known as oligodendroglia that lay down the myelin. All cell membranes...

The ionic selectivity of voltagegated channels

Another essential feature is that every type of ion channel should be capable of a marked discrimination in favour of Na+, K+ or Ca2+ ions. Appropriate selectivity filters are invariably located in an extracellular pore region of the channel into which are tucked the four links between the outer ends of the S5 and S6 segments. The first successful X-ray crystallographical study of any part of an ion channel has recently been carried out by Doyle et a .(1998) on the structure of the potassium...

Nonmyelinated nerve fibres

Vertebrates have two main types of nerve fibre, the larger fast-conducting axons, 1 to 25 fxm in diameter, being myelinated, and the small slowly conducting ones (under 1 fxm) being non-myelinated. Most of the fibres of the autonomic system are non-myelinated, as are peripheral sensory fibres subserving sensations like pain and temperature where a rapid response is not required. Almost all invertebrates are equipped exclusively with non-myelinated fibres, but where rapid conduction is called...

The relation between sarcomere length and isometric tension

The suggestion that contraction depends on the interaction of the actin and myosin filaments at the cross-bridges implies that the isometric tension should be proportional to the degree of overlap of the filaments. In order to test this idea it is necessary to measure the active increment of isometric tension at different known sarcomere lengths. The measurements have to be done on a single fibre and there are some technical difficulties because sarcomeres at the ends of a fibre may take up...

The active transport of ions

The Donnan equilibrium hypothesis required that the muscle membrane should be completely impermeable to sodium. When the radioactive isotope 24Na became available, this was soon found not to be so, for about half of the intracellular sodium in the fibres of a frog's sartorius muscle turned out to be exchanged with the sodium in the external medium in the course of one hour. Moreover, experiments on giant axons from squid and cuttlefish showed that after dissection there was a steady gain of...

Synaptic excitation in motoneurons

Motoneurons are the nerve cells which directly innervate skeletal muscle fibres. Their cell bodies lie in the ventral horn of the spinal cord, and their axons pass out to the peripheral nerves via the ventral roots. The cell body, or soma, is about 70 fxm across, and extends into a number of fine branching processes, the dendrites, which may be up to 1 mm long. The surface of the soma and dendrites is covered with small presynaptic nerve terminals, and these regions of contact show the typical...

Factors affecting the threshold for excitation

As seen, for example, in Fig. 2.7, excitation of a nerve fibre involves the rapid depolarization of the membrane to a critical level normally about 15 mV less negative than the resting potential. The critical level for excitation is the membrane potential at which the net rate of entry of Na+ ions becomes exactly equal to the net rate of exit of K+ ions plus a small contribution from an entry of Cl- ions. Greater depolarization than this tips the balance in favour of Na+, and the regenerative...

The sodium hypothesis

Cole and Curtis's results were not wholly unexpected, because it had long been supposed that there was some kind of collapse in the selectivity of the membrane towards K+ ions during the impulse. However, a year or two later both they and Hodgkin and Huxley succeeded in recording internal potentials for the first time, and it became apparent that, as has been seen in Fig. 2.4, the Fig. 4.1. Wheatstone bridge circuit used for the measurement of resistance and capacitance in parallel. Fig. 4.2....

The cardiac action potential

Intracellular recordings from heart muscle fibres were first made using isolated bundles of Purkinje fibres from dogs. The Purkinje fibres form a spe- Fig. 11.1. Mammalian heart muscle cells. Fig. 11.1. Mammalian heart muscle cells. Fig. 11.2. The cardiac action potential. Based on the action potentials produced spontaneously in isolated Purkinje fibres. Fig. 11.2. The cardiac action potential. Based on the action potentials produced spontaneously in isolated Purkinje fibres. cialized...

Electrophysiological recording methods

Axon Squid

Although the nervous impulse is accompanied by effects that can under specially favourable conditions be detected with radioactive tracers, or by optical and thermal techniques, electrical recording methods normally provide much the most sensitive and convenient approach. A brief account is therefore necessary of some of the technical problems that arise in making good measurements both of steady electrical potentials and rapidly changing ones. In order to record the potential difference...

Isometric twitch and tetanus

Isometric Lever

When a single high intensity stimulus is applied to a muscle arranged for isometric recording, there is a rapid increase in tension which then decays away Fig. 9.4 . This is known as a twitch. The duration of the twitch varies from muscle to muscle, and decreases with increasing temperature. For a frog sar-torius at 0 C, a typical value for the time between the beginning of the contraction and its peak value is about 200 ms, tension falling to zero again within 800 ms. If a second stimulus is...

Extracellular recording of the nervous impulse

There are many experimental situations where it is impracticable to use intra-cellular electrodes, so that the passage of impulses can only be studied with the aid of external electrodes. It is therefore necessary to consider how the picture obtained with such electrodes is related to the potential changes at membrane level. Since during the impulse the potential across the active membrane is reversed, making the outside negative with respect to the inside, the active region of the nerve...

Saltatory conduction in myelinated nerves

Anaesthetic Effects Nerve Impulses

In 1925 Lillie suggested that the function of the myelin sheath in vertebrate nerve fibres might be to restrict the inward and outward passage of local circuit current to the nodes of Ranvier, so causing the nerve impulse to be propagated from node to node in a series of discrete jumps. He coined the term saltatory conduction for this kind of process, and supported the idea with some ingenious experiments on his iron wire model. An iron wire immersed in nitric acid of the right strength...