Skeletal muscles are innervated by motor nerves. Excitation of the motor nerve is followed by excitation and contraction of the muscle. Thus excitation of one cell, the nerve axon, produces excitation of another cell which it contacts, the muscle fibre. The region of contact between the two cells is called the neuromuscular junction. The process of the transmission of excitation from the nerve cell to the muscle cell is called neuromuscular transmission. This chapter is concerned with how this process occurs.

Regions at which transfer of electrical information between a nerve cell and another cell (which may or may not be another nerve cell) occurs are known as synapses, and the process of information transfer is called synaptic transmission. Neuromuscular transmission is just one form of synaptic transmission; we shall examine the properties of some other synapses in the following chapter.

The neuromuscular junction

Each motor axon branches so as to supply an appreciable number of muscle fibres. Figure 7.1 shows the arrangement in most of the muscle fibres in the frog. Each axon branch loses its myelin sheath where it contracts the muscle cell and splits up into a number of fine terminals which run for a short distance along its surface. The region of the muscle fibre with which the terminals make contact is known as the end-plate. Structures and events occurring in the axon are called pre-synaptic, whereas those occurring in the muscle cell are called post-synaptic.

Nervous systems

One of the characteristics of higher animals is their possession of a more or less elaborate system for the rapid transfer of information through the body in the form of electrical signals, or nervous impulses. At the bottom of the evolutionary scale, the nervous system of some primitive invertebrates consists simply of an interconnected network of undifferentiated nerve cells. The next step in complexity is the division of the system into sensory nerves responsible for gathering incoming information, and motor nerves responsible for bringing about an appropriate response. The nerve cell bodies are grouped together to form ganglia. Specialized receptor organs are developed to detect every kind of change in the external and internal environment; and likewise there are various types of effector organ formed by muscles and glands, to which the outgoing instructions are channelled. In invertebrates, the ganglia which serve to link the inputs and outputs remain to some extent anatomically separate, but in vertebrates the bulk of the nerve cell bodies are collected together in the central nervous system. The peripheral nervous system thus consists of afferent sensory nerves conveying information to the central nervous system, and efferent motor nerves conveying instructions from it. Within the central nervous system, the different pathways are connected up by large numbers of interneurons which have an integrative function.

Certain ganglia involved in internal homeostasis remain outside the central nervous system.

Muscle cells have become adapted to a variety of different functions during their evolution, so that in other muscle types the details of the contractile process and its control show differences from those in vertebrate skeletal muscles. These final two chapters successively examine the properties of mammalian heart and smooth muscle.

Structure and organization of cardiac cells

Cardiac cells are considerably smaller than skeletal muscle fibres; they are typically up to 10 μm in diameter and 200 μm in length (Figure 12.1). However, adjacent cardiac cells are mechanically and electrically coupled both in a branched and in an end-to-end manner by intercalated disks to give a syncytium through which both electrical activity and mechanical forces are transmitted (Figure 12.1a). Atrial and ventricular myocytes specialized to generate mechanical activity contain contractile elements whose structure is similar to that found in skeletal muscle. Thus they also show thick myosin and thin actin filaments aligned transversely (Figure 12.1b). Cardiac myocytes are accordingly cross-striated in appearance. They similarly contain mitochondria, sarcoplasmic reticulum and transverse tubules. However, the sarcoplasmic reticulum is less developed. In the ventricle, it makes complexes with transverse tubular membrane at dyad rather than triad junctions. In atrial myocytes, the transverse tubular system is considerably less developed, and sarcoplasmic reticulum makes junctions at caveolae in the membrane surface. However, there are additional cardiac cell types with differing specializations that include cells that primarily generate and conduct electrical impulses.

Smooth, unstriated muscle forms the muscular component in the walls of hollow organs such as the gastrointestinal tract, the trachea, bronchi and bronchioles of the respiratory system, blood vessels in the cardiovascular system and the urogenital system. Smooth muscle contracts and relaxes much more slowly than skeletal muscle, but is much better adapted to sustained contractions. The load against which smooth muscle works is typically the pressure within the tubular structures that they line. In organs such as the blood vessels, they are responsible for a steady intraluminal pressure brought about by their tonic contraction. In the gastrointestinal tract, they produce a phasic contraction that propels its contents onward. They also occur in the iris, ciliary body and nictitating membrane in the eye, and are the small muscles which erect the hairs. The functions of smooth muscle in the body are thus diverse. This is reflected in their wide variations in structure and detailed physiological properties, for which this chapter only provides a brief introduction.

Structure

Smooth muscle cells (Figure 13.1) are uni-nucleate, elongated, often spindle-shaped and much smaller than the multi-nucleate skeletal muscle fibres. They are typically 3–5 μm in diameter and up to 400 µm long. Their thick myosin and thin actin filaments are arranged longitudinally in the cytoplasm, but are not aligned transversely. The cells consequently show no visible striations or sarcomeres. The actin filaments are attached in bundles at dense bodies in the cytoplasm, and to attachment plaques at the membrane.

Initiation of movement, whether in the form of voluntary action by skeletal muscle, or the contraction of cardiac or smooth muscle, is the clearest observable physiological manifestation of animal life. It inevitably involves activation of contractile tissue initiated or modulated by altered activity in its nerve supply. An appreciation of the function of nerve and muscle, and of the relationships between them is thus fundamental to our understanding of the function of the human body.

This book provides an introductory account of this important aspect of physiology, in a form suitable for students taking university courses in physiology, cell biology or medicine. It seeks to give a straightforward account of the fundamentals in this area, whilst including some of the experimental evidence upon which our conclusions are based.

This fourth edition includes new material reflecting the exciting discoveries concerning the ion channels involved in electrical activity, the activation of skeletal muscle and the function of cardiac and smooth muscle, reflecting important new developments made in these rapidly growing fields. We are grateful for expert advice and specialist comments from Drs. James Fraser, Ian Sabir and Juliet Usher-Smith, Physiological Laboratory, Cambridge, and Thomas Pedersen, Department of Physiology, University of Aarhus, and continue to benefit from the insight and wisdom left us by the late David Aidley, in these revisions.

The functioning of the nervous system depends largely on the interactions between its constituent nerve cells, and these interactions take place at synapses. In most cases synaptic transmission is chemical in nature, so that, as in neuromuscular transmission, the pre-synaptic cell releases a chemical transmitter substance which produces a response in the post-synaptic cell. There are a few examples of electrically transmitting synapses, which we shall consider briefly at the end of this chapter.

Acetylcholine is only one of a range of different neurotransmitters. Figure 8.1 shows some of the variety found in the central nervous system. For a long time it was thought that any one cell would only release one neurotransmitter, but several cases where two of them are released at the same time are now known.

Different chemically transmitting synapses differ in the details of their anatomy, but some features are common to all of them. In the pre-synaptic terminal the transmitter substance is packaged in synaptic vesicles. The pre- and post-synaptic cells are separated by a synaptic cleft into which the contents of the vesicles are discharged. There are specific receptors for the neurotransmitter on the post-synaptic membrane.

Just as with the neuromuscular junction, our knowledge of how synapses work was greatly affected by the invention of the intracellular microelectrode. Much of the fundamental work with this technique was performed by J. C. Eccles and his colleagues on the spinal motoneurons of the cat, so it is with these that we shall begin our account of synapses between neurons.

The impedance change during the spike

An important landmark in the development of theories about the mechanism of conduction was the demonstration by Cole and Curtis in 1939 that the passage of an impulse in the squid giant axon was accompanied by a substantial drop in the electrical impedance of its membrane. The axon was mounted in a trough between two plate electrodes connected in one arm of a Wheatstone bridge circuit (Figure 4.1) for the measurement of resistance and capacitance in parallel. The output of the bridge was displayed on a cathode-ray oscilloscope, and Rv and Cv were adjusted to give a balance, and therefore zero output, with the axon at rest. When the axon was stimulated at one end, the bridge went briefly out of balance (Figure 4.2) with a time course very similar to that of the action potential. The change was shown to be due entirely to a reduction in the resistance of the membrane from a resting value of about 1000 Ω cm2 to an active one in the neighbourhood of 25 Ω cm2. The membrane capacitance of about 1 µF/cm2 did not alter measurably.

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.

Summary

Memory for the final position of a previously viewed target is often displaced in the direction of target motion. This forward displacement has been referred to as representational momentum (Freyd & Finke 1984) and is influenced by numerous variables (Hubbard 1995b, 2005). Although initial studies of representational momentum appeared consistent with the hypothesis that observers internalize or incorporate the principle of momentum into the representation of the target, subsequent studies reported displacement inconsistent with such a literal internalization or incorporation of momentum. For example, variables other than implied momentum such as conceptual knowledge about target identity (Reed & Vinson 1996), expectations regarding future target motion (Verfaillie & d'Ydewalle 1991; Johnston & Jones 2006), attributions about the source of target motion (Hubbard & Ruppel 2002; Hubbard & Favretto 2003), and whether observers visually track the target (Kerzel 2000; Kerzel et al. 2001) influence displacement.

Summary