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A nociceptor has been defined as a receptive ending that is activated by noxious (tissue threatening, subjectively painful) stimuli, is capable by its response behaviour of distinguishing between innocuous and noxious events, and encodes the intensity of noxious stimuli. When tested with graded natural stimuli (mechanical, chemical, thermal), these receptors do not respond to stimuli such as that which occurs during the normal activity of the muscle but rather it requires noxious intensities of stimulation for activation. A liminal activation of a muscle nociceptor may occur if the intensity of stimulation approaches noxious levels without damaging the tissue. Teleologically, this property is important, since a nociceptor is supposed not only to signal tissue damage but also to prevent its occurrence.

This is a tutorial chapter, mainly aiming to introduce the neuromuscular system. Treated items include basic aspects of skeletal muscle and peripheral axon physiology, principles of sensory and motor muscle innervation, and (very briefly) some general points concerning motor functions of the central nervous system. For muscles, items include: muscle metabolism, excitation-contraction coupling, and the mechanisms for force generation. For axons, items include: intra-axonal transport processes, membrane properties, and the mechanisms and speed of the axonal conduction of action potentials (spikes). The different motor unit and muscle fibre types of limb muscles are introduced and a brief description is given of electromyographic techniques for recording motor unit activity.

In the opening decades of the 20th century, there would be new ways of thinking about how neurons communicate with each other and how they stimulate muscles. The earlier idea of a continuous, unbroken electrical wave shooting from one neuron to another would be challenged by the notion of chemicals, called neurotransmitters, being released at synapses. What led scientists to conclude that axon endings liberate chemicals to stimulate or inhibit other cells? And what were some of the early ramifications of this important discovery? The answers to these questions can be appreciated only by looking at the fives of two very different 20th-century scientists, Otto Loewi and Henry Dale. This chapter looks at the work of Loewi and Dale on neurotransmitters, adrenalin, autonomous nervous system, chemical transmission, ergot, noradrenaline, acetylcholine, and skeletal muscles.

This chapter discusses the function of respiratory muscles and their interaction with the respiratory system in health and disease. Dyspnoea generally occurs when the load on the respiratory muscle pump exceeds its capacity. It also occurs when respiratory muscle weakness, abnormalities in the respiratory muscle control, and irregularities in the skeletal muscle occur. The chapter begins with a discussion on the respiratory muscle in healthy individuals and then examines its contribution to breathlessness in disease. Respiratory muscle functions that may contribute to breathlessness include respiratory muscle weakness, respiratory movement disorder, COPD, and chronic heart failure (CHF). The chapter also provides a brief discussion on respiratory muscle function in cancer patients.

This chapter identifies four attempts to create a successor theory and to accept the new findings of experiment and microscopy during the 17th century. It first studies Francis Glisson, who is known for his work on rickets and his research on the true function of the liver. Next, it takes a look at William Croone, who published his enquiries into the movement of skeletal muscle in De ratione motus musculorum, and Giovanni Borelli, whose intromechanics can be related to the physiology of the animal spirit. The chapter ends with a discussion on Thomas Willis, whose Cerebri anatome is considered by some to be the foundation work of neurology.

This chapter outlines an empirical resolution of charge movements into a number of individual components. Many independent procedures have been used to demonstrate various charge-movement components and to characterize them. Attempts to demonstrate individual components have been primarily focused on the non-linear charge. The steady-state charge-voltage curve does not assume a simple sigmoid shape about an inflection voltage. Some of the kinetic features of the slow transitions resemble those shown by potassium-channel gating. The hump waveforms are observed in amphibian twitch muscle and can also be demonstrated in heavily averaged records from frog slow pyriformis muscle fibres, whose membranes lack potassium channels. The charge fractionation by a combination of independent electrical and pharmacological criteria strongly suggests that the most prominent portion of the intramembrane charge (charge I) consists of at least two physically distinct components of non-linear charge. Charge-movement components are also characterized through their sensitivity to different pharmacological agents. The pharmacological studies yield an independent charge separation. An analysis of the interactions between the influences of tetracaine, caffeine and the potential across the transverse tubular membrane on contraction suggests an action at a common site. Local anaesthetics can be useful in the characterization of the steady-state and kinetic properties of individual components within charge I. A complementary pharmacological separation of non-linear charge is accomplished using large rather than small voltage steps. In the cut fibres, the measured intramembrane charge varies considerably less steeply with voltage than has been reported for intact fibres. When corrections are made for the membrane currents that flow under the Vaseline seals in addition to the currents which arise from the central pool region of the recording system, cut fibres show an asymmetrical dependence of the non-linear charge upon the voltage.

This chapter explores the capacitative properties of biological membranes and provides ways to measure the membrane capacitance in striated muscle. The capacitance of a bilayer is inversely related to the chain length of its constituent hydrocarbons, and the latter is in turn proportional to bilayer thickness. The nature of the polar head groups does not greatly affect membrane capacitance. Skeletal muscle membranes form a network of 50-nm diameter branching tubules penetrating into the fibre whose lumina are continuous with extracellular fluid. Such a system would intrinsically have particular capacitative properties. Using the Laplace transform, a square-root relationship between membrane impedance properties and the input parameters is found. The ‘lumped’ four-component model offers the simplest available electrical description of striated muscle membrane geometry. In contrast, distributed models represent the transverse tubules as a cable system that allows radial voltage differences. Lattice models have proven useful in both the interpretation of the measurements of linear capacitances and the localization of non-linear charge to different regions of membrane. The chapter also discusses voltage-clamp methods for studying the dielectric properties of skeletal muscle. Each voltage-clamp method has characteristic advantages and limitations. The most appropriate equivalent circuit to represent the transverse tubular system remains incompletely resolved. The cable properties of tubular membrane necessitate an operational definition of measured effective capacitance arising from an application of the properties of the Laplace transform to a general circuit network. The studies suggest that, at least through the frequency range over which charge movements have been measured, the effective capacitance accurately reflects the properties of the actual electrical elements of surface or tubular membrane, given appropriate bathing solutions and voltage-clamp geometry.

This chapter explores the possible causal relationship relation between charge species in the membrane of skeletal muscle, which many studies have investigated. It may be suggested that any physiological activation is accompanied by a transfer of charge. In fully polarized, cut skeletal muscle fibres also, the onset of mechanical activation is associated with a constant overall charge transfer. This constancy is held through applied steps, and persists even when the simple applied steps are replaced by pulse procedures in which the final voltage is reached via a pre-pulse. This gives the evidence that a single reaction sequence reflected in the entire measured intramembrane charge regulated contractile activation. This equivalence between charge transfer and contraction breaks down under a number of conditions. Studies in cut fibres defining charge in terms of steady-state properties suggest that the alterations in conditions of intracellular Ca²⁺ do not affect steady-state charge movement. Independent intramembrane components could undergo separate and parallel transitions in response to voltage change. A number of kinetic experiments also throw light on possible causal relationships between charge-movement components. Independent intramembrane components can also undergo separate and parallel transitions in response to voltage change. In the simplest form of such a model, each component of charge transfer could be directly coupled to activation of each physiological process. Studies of OFF currents can also be used to dissociate changes in the components of intramembrane charge.

This chapter explores applications of equilibrium thermodynamics and statistical principles to the derivation of some limiting properties expected for a capacitative charge in an electric field. The statistical approach determines the relationship between the microscopic and macroscopic properties of the charge movement, through deduction of the partition function for each system from experimental properties. A number of attempts have been made to describe the more complex behaviour of the intramembrane charge in skeletal muscle. The simplest two-state, constant-dipole model assumes a population of membrane macromolecules undergoing configurational changes in response to voltage change. More general N-state systems can also be formulated using known properties of the canonical ensemble of statistical mechanics. The general relationships between membrane capacitance and partition functions that emerge characterize the microscopic states available to each system and their relative occupancies at different voltages. It also leads to the prediction of a number of limiting properties concerning charge conservation and saturation at large absolute imposed membrane potentials, and the prediction that the steepest voltage dependence of the non-linear charge would arise from systems of high valency and few rather than many states. The current view for membrane structure suggests that a constant number of integral proteins are individually embedded in the lipid bilayer. Statistical mechanics treats each protein molecule as a subsystem separated from and consequently independent of the remaining canonical ensemble of other subsystems. Charge movements can be viewed as the consequence of configurational changes in individual subsystems in response to membrane potential change. The component subsystems redistribute among their available microstates owing to the dependence of their energies on the applied electric field.