The renal nerves are the communication link between the central nervous system and the kidney. In response to multiple peripheral and central inputs, efferent renal sympathetic nerve activity is altered so as to convey information to the major structural and functional components of the kidney, the vessels, glomeruli, and tubules, each of which is innervated. At the level of each of these individual components, information transfer occurs via interaction of the neurotransmitter released at the sympathetic nerve terminal-neuroeffector junction with specific postjunctional receptors coupled to defined intracellular signaling and effector systems. In response to normal physiological stimuli, changes in efferent renal sympathetic nerve activity contribute importantly to homeostatic regulation of renal blood flow, glomerular filtration rate, renal tubular epithelial cell solute and water transport, and hormonal release. Afferent input from sensory receptors located in the kidney participates in this reflex control system via renorenal reflexes that enable total renal function to be self-regulated and balanced between the two kidneys. In pathophysiological conditions, abnormal regulation of efferent renal sympathetic nerve activity contributes significantly to the associated abnormalities of renal function which, in turn, are of importance in the pathogenesis of the disease.

Neural Control Of Renal Function

Section I-Peripheral Nerve.- 1 Peripheral Nerve Structure.- 1. Introduction.- 2. Histology and Development.- 3. The Axon.- 3.1. Filaments and Microtubules.- 3.2. Other Organelles and the Axolemma.- 4. Sheaths of Axons.- 4.1. Schwann Cells.- 4.2. Myelin.- 4.3. Function of Schwann Cells and Their Myelin Sheaths.- 4.4. Connective Tissue Sheaths.- 5. References.- 2 The Nerve Impulse.- 1. Introduction.- 2. Passive Electrical Properties.- 3. Voltage-Clamp Analysis of the Ionic Current.- 4. Momentary Current-Voltage Relations.- 5. The Threshold Conditions for Excitation.- 6. Factors Determining Conduction Velocity.- 7. References.- 3 Axoplasmic Transport-Energy Metabolism and Mechanism.- 1. Introduction.- 2. Fast Axoplasmic Transport.- 2.1. Characterization.- 2.2. Mechanism and Energy Supply.- 2.3. Transport and Membrane Function.- 3. Slow Axoplasmic Transport.- 3.1. Characterization.- 3.2. Mechanism.- 4. References.- Section IIA-Junctional Transmission-Structure.- 4 Neuromuscular Junctions and Electric Organs.- 1. Introduction.- 2. The Typical Neuromuscular Junction.- 2.1. Distribution and Location of Nerve Terminals.- 2.2. The Axon.- 2.3. The Synaptic Space.- 2.4. Postjunctional Muscle Fiber.- 3. Variations of Motor End Plates.- 3.1. Variations from Class to Class.- 3.2. Endings on Slow-Twitch and Rapid-Twitch Fibers.- 3.3. Endings on Slow Tonic Muscle Fibers.- 4. Electric Organs.- 4.1. Electrocytes.- 4.2. Innervation and Ultrastructure.- 5. References.- 5 The Peripheral Autonomic System.- 1. Anatomical Considerations: Sympathetic and Parasympathetic Divisions.- 2. Morphological Observations.- 2.1. Preganglionic Neurons.- 2.2. Postganglionic Neurons.- 2.3. Adrenal and Extra-Adrenal Chromaffin Cells.- 3. References.- 6 Ultrastructure of Ganglionic Junctions.- 1. General Considerations.- 2. Sympathetic Ganglia.- 2.1. Amphibia.- 2.2. Reptiles.- 2.3. Mammals.- 2.4. Some Effects of Different Fixatives.- 3. Parasympathetic Ganglia.- 3.1. Ciliary Ganglion.- 3.2. Otic Ganglion.- 3.3. Ganglia of the Enteric Plexuses.- 3.4. Cardiac Ganglion Cells.- 4. Summary and Comment.- 5. References.- Section IIB-Junctional Transmission-Function.- 7(i) Neuromuscular Transmission-Presynaptic Factors.- 1. Synthesis, Storage, and Release of Acetylcholine.- 1.1. Synthesis of ACh.- 1.2. Storage and Release.- 2. The Acceleration of Release by Nerve Impulses.- 2.1. The Role of the Nerve Impulse.- 2.2. The Role of Ca2+.- 2.3. After- Effects of Depolarization-Secretion Coupling.- 3. References.- 7 (ii) Neuromuscular Transmission-The Transmitter-Receptor Combination.- 1. Introduction.- 2. Molecular Basis of Chemoelectric Transduction.- 3. Pharmacology.- 4. Chemical Nature of the Acetylcholine Receptor.- 5. Desensitization.- 6. References.- 7 (iii) Neuromuscular Transmission-Enzymatic Destruction of Acetylcholine.- 1. Location and Measurement of Cholinesterases at the Junction.- 1.1. Histochemical Staining.- 1.2. Microchemical Methods.- 1.3. Assay of External AChE.- 1.4. Radioautographic Methods.- 2. Amounts and Types of Cholinesterase at the Junctions.- 3. Requirement for AChE in Impulse Transmission.- 4. Relation of AChE to ACh- Receptors.- 5. Quantitative Relation of AChE to ACh at the End Plate.- 6. References.- 8 Ganglionic Transmission.- 1. Introduction.- 2. Response of Autonomic Ganglia to Preganglionic Volleys.- 2.1. Response of Normal Ganglia.- 2.2. Response of Curarized Ganglia.- 2.3. Slow Ganglionic Responses and Afterdischarges.- 3. Electrical Constants of Ganglion Cell Membrane.- 4. Action Potentials of Single Ganglion Cells.- 4.1. Response to Antidromic Stimulation.- 4.2. Response to Direct Intracellular Stimulation.- 4.3. Response to Orthodromic Stimulation.- 4.4. Ionic Requirement for Generation of Action Potential.- 5. Nature and Electrogenesis of Postsynaptic Potentials.- 5.1. The "Fast" Excitatory Postsynaptic Potential.- 5.2. The "Slow" Excitatory Postsynaptic Potential.- 5.3. The "Late Slow" Excitatory Postsynaptic Potential.- 5.4. The "Slow" Inhibitory Postsynaptic Potential.- 6. Cholinergic and Adrenergic Receptors at Preganglionic Nerve Terminals.- 6.1. Cholinergic Receptor Site.- 6.2. Adrenergic Receptor Site.- 7. References.- 9 Function of Autonomic Ganglia.- 1. Introduction.- 2. Ganglia as Coordinating Centers.- 2.1. The Relay Hypothesis of Ganglionic Function.- 2.2. Development of a Stochastic Hypothesis.- 3. Experimental Evidence.- 3.1. Observed Patterns of Innervation.- 3.2. Ganglionic Activity and Factors Influencing It.- 3.3. Relative Autonomy of Ganglia.- 4. Conclusions.- 5. References.- 10 Peripheral Autonomic Transmission.- 1. Introduction.- 2. Definition of the Autonomic Neuromuscular Junction.- 2.1. Relation of Nerve Fibers to Muscle Effector Bundles.- 2.2. Relation of Nerve Fibers to Individual Smooth Muscle Cells.- 3. Adrenergic Transmission.- 3.1. Introduction.- 3.2. Structure of Adrenergic Neurons and Storage of Noradrenaline.- 3.3. Electrophysiology of Adrenergic Transmission.- 3.4. Ionic Basis of the Action of Catecholamines on the Postjunctional Membrane.- 3.5. Summary.- 4. Cholinergic Transmission.- 4.1. Introduction.- 4.2. Localization of Acetylcholinesterase.- 4.3. Electrophysiology of Cholinergic Transmission.- 4.4. Ionic Basis of the Action of ACh on the Postjunctional Membrane.- 4.5. Summary.- 5. Purinergic Transmission.- 5.1. Introduction.- 5.2. Electrophysiology of Purinergic Transmission.- 5.3. Summary.- 6. Conclusions.- 7. References.- 11 "Trophic" Functions.- 1. Introduction.- 2. Regulation of Taste Buds.- 3. Regulation of Amphibian Limb Regeneration.- 4. Regulation of Physiological and Metabolic Properties of Muscle.- 4.1. Resting Membrane Potential.- 4.2. Acetylcholine Sensitivity.- 4.3. Cholinesterase Activity.- 4.4. The Role of ACh Release.- 4.5. The Dynamic Nature of the Muscle Fiber.- 4.6. Plasticity of the Motor Unit.- 5. Mechanisms of Neural Regulation.- 6. References.- Section III-Receptors-Structure and Function.- 12 Cutaneous Receptors.- 1. Introduction.- 2. Morphology of Cutaneous Nerves.- 2.1. Uniformity of Cutaneous Axons.- 2.2. Relative Numbers of Myelinated and Nonmyelinated Axons.- 3. Morphology of Cutaneous Receptors.- 3.1. Encapsulated Receptors.- 3.2. Unencapsulated Corpuscular Receptors.- 3.3. Noncorpuscular Receptors.- 4. Physiology of Cutaneous Receptors.- 4.1. Cutaneous Mechanoreceptors.- 4.2. Cutaneous Thermoreceptors.- 4.3. Nociceptors.- 5. References.- 13 The Pacinian Corpuscle.- 1. Introduction.- 2. Morphology.- 3. Afferent Responses to Mechanical Stimuli.- 4. Mechanical Properties of the Corpuscle.- 5. Receptor Potentials.- 6. Impulse Activity in the Nerve Terminal.- 7. Distribution of Pacinian Corpuscles.- 8. Central Effects of Impulses from Pacinian Corpuscles.- 9. References.- 14 Receptors in Muscles and Joints.- 1. Introduction.- 2. Joint Receptors.- 3. Tendon Organs.- 4. Muscle Spindles.- 4.1. Reptiles.- 4.2. Amphibia.- 4.3. Birds.- 4.4. Mammals.- 5. Uncertain Origin of Adaptation.- 6. References.- 15 Enteroceptors.- 1. Introduction.- 2. Methods.- 2.1. Histology.- 2.2. Physiology.- 3. Cardiovascular Receptors.- 3.1. Systemic Arterial Baroreceptors.- 3.2. Pulmonary Arterial Baroreceptors.- 3.3. Ventricular Receptors.- 3.4. Atriovenous Receptors.- 4. Respiratory System Receptors.- 4.1. Cough and Irritant Receptors.- 4.2. Pulmonary Stretch Receptors.- 4.3. Type J Receptors.- 4.4. Other Receptors.- 5. Alimentary System Receptors.- 5.1. Muscular Receptors.- 5.2. Serosal Receptors.- 5.3. Muscularis Mucosae Receptors.- 5.4. Chemoreceptors.- 5.5 Hepatic Osmoreceptors.- 6. Urinary Tract Receptors.- 6.1. Bladder.- 6.2. Urethra.- 7. Other Enteroreceptors.- 8. References.- 16 Arterial Chemoreceptors.- 1. Introduction.- 2. Structure.- 2.1. Light Microscopy.- 2.2. Electron Microscopy.- 2.3. Degeneration Studies.- 3. Function.- 3.1. Types of Activity in the Nerve Supply to the Receptor Complex.- 3.2. The Type I Cell.- 4. The Identity of the Receptor.- 4.1. The Received View.- 4.2. A New Hypothesis.- 5. References.- 17 Taste Receptors.- 1. Introduction.- 2. Gustatory Nerve Fiber Response to Chemical Stimuli.- 2.1. Multiple Sensitivity of Single Chorda Tympani Fibers.- 2.2. Neural Code for Quality of Taste and "Across-Fiber Pattern" Theory.- 3. Electrical Responses of Gustatory Cells to Chemical Stimuli.- 3.1. Innervation and Structure of Taste Bud.- 3.2. How Do Gustatory Cells Respond to Chemical Stimuli?.- 4. References.

The Peripheral Nervous System

The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure.

Neural control of renal function.

Publisher Summary This chapter discusses the applications of tetrodotoxin, saxitoxin, and related substances in neurobiology. Tetrodotoxin is not unique in its action; saxitoxin appears to possess very similar pharmacological properties; and a number of other substances are related chemically and pharmacologically. The usefulness of tetrodotoxin depends upon its ability to suppress the action potentials in skeletal muscles and in vertebrate nerves. It acts on these tissues in a highly specific manner, preventing the voltage-dependent, regenerative increase of permeability to sodium ions. The evidence that saxitoxin has very similar actions is scanty, but adequate. In general, the actions of tetrodotoxin and saxitoxin resemble each other. Most of the experimental analyses of the actions of these toxins in blocking the early transient channels in nerve and muscle cell membrane are carried out using invertebrate giant fibers.

Tetrodotoxin, Saxitoxin, and Related Substances: Their Applications in Neurobiology

Myofascial pain syndrome (MPS) is described as the muscle, sensory, motor, and autonomic nervous system symptoms caused by stimulation of myofascial trigger points (MTP). The participation of fascia in this syndrome has often been neglected. Several manual and physical approaches have been proposed to improve myofascial function after traumatic injuries, but the processes that induce pathological modifications of myofascial tissue after trauma remain unclear. Alterations in collagen fiber composition, in fibroblasts or in extracellular matrix composition have been postulated. We summarize here recent developments in the biology of fascia, and in particular, its associated hyaluronan (HA)-rich matrix that address the issue of MPS.

Fascial Components of the Myofascial Pain Syndrome

1. Adaptation in terms of the early fall of the receptor potential was studied in isolated frog spindles. The contribution of gross mechanical changes to the decline of the response was determined by comparing the responses obtained under constant length and under constant tension.

2. It was found that the early adaptation under constant stretch increased with increasing lengthening of the spindle for stretches up to 25-30% of the resting length and decreased with still stronger stretches. When the spindle was stretched by 100% or more the static phase of the receptor potential reached nearly the same height as the dynamic peak and the early adaptation approached zero.

3. The early adaptation decreased with decreasing velocity of linearly rising stretch and approached zero for stretches below about 0·5 mm/sec.

4. For different strengths of a steplike stretch the amount of early adaptation was linearly related to the fall in tension over the same period. The relative amount of tension fall, however, was always less than the corresponding fall of the response.

5. The early adaptation was 15-20% smaller under constant tension than under constant length for stretches below the level giving the maximum dynamic peak.

6. The results suggest that a comparatively small amount of the early adaptation of the spindle response to constant stretch is related to gross alterations in length in different regions of the spindle. The main part of the adaptive fall of the response is probably related to functional properties of the sensory membrane and to the ionic mechanism underlying the production of the receptor potential.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1971.sp009343

The contribution of mechanical factors to the early adaptation of the spindle response

1. Effects of changes in ionic environment on the receptor potential were studied in isolated frog spindle. Particular attention was focused on the action of potassium removal on the early adaptive decline of the response.

2. Removal of potassium caused a reduction and final disappearance of the dynamic overshoot of the receptor potential. The static phase of the response was also reduced although to less extent. The repolarization phase of the response following release of phasic or maintained stretch was greatly prolonged.

3. Increased potassium concentration caused a reduction of the response, but did not change its general time course. The amount of reduction was related to the potassium concentration.

4. Removal of sodium caused a marked diminution of the response, the static phase being in general more affected than the dynamic phase.

5. It is suggested that the effects of potassium removal are caused by a delay in sodium inactivation and a partial depolarization of the endings. It is concluded that the greater part of the early adaptation of the spindle proper may be attributed to ionic mechanisms in the transducer membrane.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1971.sp009616

Ionic effects on spindle adaptation

The transducer properties of the sensory endings of the muscle spindle have been studied in isolated spindles of the frog's toe muscle. The depolarization of the sensory endings during dynamic stretch at constant velocity is a rectilinear function of the amount of lengthening of the spindle, for stretches up to about 30 % of its resting length. This suggests that the dynamic phase of the stimulus is transmitted to the endings with little distortion. When the spindle is stretched by more than 30 % of its resting length a saturation phase of constant depolarization is formed. The development of this phase may be explained by the assumption that parallel elastic elements take up the load or that the sensory membrane saturates beyond a given amount of distortion.



After release of stretch the depolarization of the endings decreases exponentially with time. The time course of repolarization is considerably slower than the return of the spindle to resting length and relatively independent of the rate of release of stretch. This suggests that the repolarization is governed by the transduction process and related to the electrical proper ties of the sensory membrane.

Transducer characteristics of the muscle spindle as revealed by its receptor potential.

The tension developed in the isolated frog muscle spindle during stretch has been studied and related to the impulse response and the isolated receptor potential of the spindle. With a steplike stretch tension rose to an initial peak and then declined towards a steady level. The decay consisted of an initial phase of rapid fall and a later phase of slow decline when stretch was prolonged. The magnitude of the peak and the static level of tension were exponential functions of the amount of stretch. The response of the spindle in terms of the impulse discharge and the isolated receptor potential closely followed the tension changes during various phases of stretch. Adaptation of the spindle to maintained stretch, in terms of the fall of the receptor potential, followed the same general time course as the decay in tension. The results suggest that tension during stretch reflects structural changes within the spindle and that these changes may bear a more direct relation to the sensory response than lengthening. Neither the gross tension nor the elongation ran, however, be regarded as a dirert representation of the actual stimulus to the endings.

Relation between Tension and Sensory Response of the Isolated Frog Muscle Spindle during Stretch

THE impulse response of the muscle spindle to an applied stretch consists of a dynamic discharge during the phase of increase in length, followed by a static discharge while stretch is maintained at a steady level1–3. The underlying receptor potential shows corresponding characteristics : a rapid dynamic rise followed by a decay to a static level (Fig. 1)2,4. This differentiation of the response into two separate components may be explained as the result of structural differences between the central and the polar zones of the intrafusal muscle fibres1,5–7. The dynamic component would arise in the central zone, which seems to be the more elastic, while the static phase of the response would be generated in the more viscous polar regions. At present there is, however, no direct evidence for a mechanical differentiation of the response.

D. Ottoson

Papers

The contribution of mechanical factors to the early adaptation of the spindle response

Ionic effects on spindle adaptation

Transducer characteristics of the muscle spindle as revealed by its receptor potential.

Relation between Tension and Sensory Response of the Isolated Frog Muscle Spindle during Stretch

Changes of length within the frog muscle spindle during stretch as shown by stroboscopic photomicroscopy.