INTRODUCTION

Skeletal muscle is one of the most abundant and adaptable tissues in the human body. The heterogeneity and plasticity of mammalian muscle have become major topics of interest (Pette & Staoron 1997, Pette & Vrbová 1992). In the past two decades, the physiological mechanisms that influence the neural adaptations that accompany and contribute to these changes in skeletal muscles have been under increasing scrutiny (Gandevia 2001). They are gradually being recognized as playing a key role in evaluating the efficacy of therapeutic interventions (Enoka 1997, Pette & Vrbová 1999). This chapter outlines basic muscle and peripheral nerve physiology. Particular attention is paid to the propagation of nerve and muscle action potentials, to differing characteristics of motor units and to the concept of nerve-muscle interaction.

MOTOR NEURON TO MUSCLE ACTIVATION

NEURAL CONTROL OF MUSCLE

Smooth, coordinated movement is the output of a complex neuromuscular system. Skeletal muscle is capable of generating varying tensions and, at its very simplest, smooth, coordinated movement depends on the practical issue of contracting the required muscles in the right sequence at the right time. The control of coordinated movement is complex as different muscles combine in a variety of patterns. Appropriate combinations of excitation or inhibition of different motor neurons in dynamic series provide the required overall functional effect. Even now, there is much to understand about the way in which the neural system devises these patterns of excitation and inhibition, about the interrelationship of the afferent and efferent neural systems, and not least about how motor units are selected to achieve a particular movement and about how firing patterns are updated as the movement evolves.

The brain uses stereotypical electrical signals – nerve action potentials – to convey information received in the central nervous system (CNS) and to encode information at various levels. The signals consist of potential changes produced by electrical currents flowing across cell membranes, currents carried by ions such as those of sodium (Na⁺), potassium (K⁺) and chlorine (Cl⁻) (see ‘Electrophysiological properties of nerves and muscles’, below). The coding of information depends principally on the frequency of impulses being transmitted along a nerve fibre, the number of fibres involved and on the synaptic connections made within the spinal cord and at higher levels of the CNS. Variability of response occurs at the level of neuronal synapses and the ability to modify processes of excitation and inhibition is thought to be critical to changes which occur in central control mechanisms.

THE MOTOR UNIT

The smallest unit of movement that the CNS can control is a motor unit. Defined by Sherrington in 1906, this unit consists of a motor neuron, together with its axon and dendrites, motor end plates and the muscle fibres it supplies. Motor neurons are the largest cells in the ventral horn of the spinal cord. The activity or firing frequency of these cells is dependent on their connections with afferent fibres from muscles, joints and skin, as well as their connections with other parts of the CNS.

Each motor neuron integrates excitatory (EPSP) and inhibitory (IPSP) postsynaptic potentials from thousands of synapses spread over the dendrites and cell body or soma, and these influence whether the motor neuron generates an action potential. When an action potential is discharged down the axon, its amplitude remains constant. The action potential is an all or nothing impulse regenerated at regular intervals along the axon until it reaches the nerve-muscle synapse. There the action potential triggers transmitter release, which in turn causes a muscle action potential and contraction of all the muscle fibres that particular axon supplies. External electrical stimulation is used therapeutically to elicit skeletal muscle contraction supplementing or enhancing normal physiological processes. To understand such uses, it is important to understand the underlying electrophysiological processes.

ELECTROPHYSIOLOGICAL PROPERTIES OF NERVES AND MUSCLES

All nerve fibres have essentially the same structure and resemble a shielded electric cable. As described by Keynes & Aidley (2001), inside there is a central long conducting cylinder of cytoplasm or axoplasm surrounded by insulation: outside is another conducting layer, the electrically excitable nerve membrane. Similarly, skeletal muscle fibres are embedded in a basal lamina – a glycoprotein and collagen layer – and have an electrically excitable cell membrane (sarcolemma) that contains the intracellular fluid (sarcoplasm) and intracellular structures. Conduction of action potentials along membranes of nerves and muscles occurs because there is a potential difference between the intracellular fluid and the extracellular fluid (Fig. 5.1). The resting potential is of the order of −90mV for skeletal muscle, and −70mV for lower motor neurons. The minus sign indicates that the inside of the cell has a negative potential relative to the exterior; this potential difference can be altered by passage of ions.

Figure 5.1 The potential difference across a cell membrane measured with an intracellular electrode and an extracellular electrode.

In the cell membranes of both nerves and muscles, protein molecules are embedded in a double layer of lipid molecules arranged with their hydrophilic heads facing outward and hydrophobic tails extending into the middle of the layer. Some protein molecules make contact with both the extracellular and the intracellular fluids; these exert control functions, with one region being a selectivity filter and another providing a gate that can be open or closed. The intracellular and extracellular fluids are in osmotic equilibrium, that is, the concentration of ions in the intracellular and extracellular fluids is similar. There is, however, a difference in the proportions of different ions in the two solutions: there is a higher concentration of K⁺ ions in the intracellular fluid, and higher concentrations of both Na⁺ and Cl⁻ ions in the extracellular fluid.

MOVEMENT OF IONS

Ions at high concentration tend to diffuse to areas of low concentration; their movement is also influenced by voltage gradients, with positive ions being attracted down the negative gradient, and vice versa. An outward movement of K⁺ ions down their concentration gradient would be expected but, at the same time, the inner surface of the membrane is at a negative potential with respect to the outside and this tends to restrain the outward movement of positively charged ions.

The equilibrium potential of any ion is proportional to the difference between the logarithms of intracellular concentration and the extracellular concentration. It is defined by the Nernst equation as the electric potential necessary to balance a given ionic concentration across a membrane so that the overall passive movement of the ion is zero.

By 1955, Hodgkin and Keynes had established that cell membranes of both muscles and nerves were permeable to K⁺ and Na⁺ ions, and that these ions are in a continuous state of flux across the membrane against both the concentration and the electrical gradients. Their findings supported the concept of an active transport system with voltage-sensitive mechanisms that uses energy supplied by the hydrolysis of adenosine triphosphate (ATP) to pump Na⁺ ions out of the cell and to accumulate K⁺ ions within the cell. Evidence suggests that the expulsion of Na⁺ ions to the influx of K⁺ ions is of the order of 3:2.

GENERATION AND PROPAGATION OF ACTION POTENTIALS

The unequal distribution of ions across the cell membrane of both nerve and muscle cells forms the basis for generation and propagation of action potentials. Nerve and muscle cells are excitable, that is, they are able to produce an action potential after the application of a suitable stimulus (see ‘Threshold’, below). An action potential is a transient reversal of the membrane potential – a depolarization. This lasts for about 1 ms in nerve cells and up to 2 ms in some muscle fibres.

Threshold

An initial opening of a few of the voltage-activated sodium channels occurs, followed by a rapid transient increase in Na⁺ permeability. This allows Na⁺ ions to diffuse rapidly into the cell, causing a sudden accumulation of positive charge on the inside surface of the neural or muscle fibre membrane. The increased permeability to Na⁺ ions is followed by repolarization via the opening of voltage-activated K⁺ channels; there is some hyperpolarization beyond the resting potential.

The nature of the regenerating mechanism was demonstrated both in terms of the time course of the action potential and of ionic conductance by Hodgkin & Huxley (1952). Stimulus below the threshold required to produce an action potential reduces, but does not reverse, the membrane potential. As the stimulus is increased, the potential difference across the cell membrane is reduced until it reaches the critical threshold level. At this level, the stimulus will lead to the automatic generation of an action potential. The level of the threshold varies according to a number of factors, including how many action potentials the nerve fibre has recently conducted.

After an action potential, two changes occur that make it impossible for the nerve fibre to transmit a second action potential immediately. First, inactivation (the absolute refractory period) occurs during the falling phase of the action potential. During this period, no amount of externally applied depolarization can initiate a second regenerative response. After the absolute refractory period, there is a relative refractory period during which the residual inactivation of the Na⁺ conductance and the relatively high K⁺ conductance combine to produce an increase in the threshold for action potential initiation.

To stimulate a nerve, the stimulus has to be both of sufficient intensity and of sufficient duration to depolarize the nerve membrane. Action potentials can be initiated in peripheral nerves by the application of suitable electrical stimuli (pulses). The rate of change and frequency of stimuli are important.