Adapting Stretch Receptors Research Articles

Pathophysiology of Airway Afferent Nerves

Abstract Vagal afferent nerves provide an airway defense mechanism which is ensured by their activation. These nerves can be activated mechanically mainly through mechanosensitive Aβ fibers which are divided into slowly adapting (SARs) and rapidly adapting stretch receptors (RARs). Chemical activation is provided by an interaction of chemical substances with specific receptors. C-fibers are highly sensitive to a direct chemical stimulation accomplished by an activation of ligand-gated ion channels. According to the large influence and mechanisms of vagal afferent nerves, there is a probability that an inappropriate activity of these nerves can cause the symptoms of the respiratory diseases, e.g. cough, dyspnoea, or airway hyperreactivity. The aim of this review is to summarize the physiology of airway afferent nerves and point out the role of vagal sensory nerves dysfunction in the pathogenesis of some respiratory diseases. The understanding of its mechanism could lead to new therapeutic strategies in patients with airway-related pathology.

Sensory structures of lungs and airways

The оptimum realization to respiratory function depends on varied sensory feedbacks from ensemble of the sources of the body. Pulmonary sensory receptors are the initiating sites for lung reflexes. The information arriving from lungs and airways information is one of the most important feedbacks that provide the adaptation of the respiratory centre for producing of the pattern optimal in terms of work and force of breathing. In article the review of currently existing data about morphology and functional characteristics of sensitive pulmonary structures is presented: slowly adapting stretch receptors, rapidly adapting receptors, C-fiber receptors and neuroepithelial bodies.

Airway nerves and dyspnea associated with inflammatory airway disease

The neurobiology of dyspnea is varied and complex, but there is little doubt that vagal nerves within the airways are capable of causing or modulating some dyspneic sensations, especially those associated with inflammatory airway diseases. A major contributor to the dyspnea associated with inflammatory airway disease is explained by airway narrowing and increases in the resistance to airflow. The autonomic (parasympathetic) airway nerves directly contribute to this by regulating bronchial smooth muscle tone and mucus secretion. In addition, a component of the information reaching the brainstem via airway mechanosensing and nociceptive afferent nerves likely contributes to the overall sensations of breathing. The airway narrowing can lead to activation of low threshold mechanosensitive stretch receptors, and vagal and spinal C-fibers as well as some rapidly adapting stretch receptor in the airways that are directly activated by various aspects of the inflammatory response. Inflammatory mediators can induce long lasting changes in afferent nerve activity by modulating the expression of key genes. The net effect of the increase in afferent traffic to the brainstem modulates synaptic efficacy at the second-order neurons via various mechanisms collectively referred to as central sensitization. Many studies have shown that stimuli that activate bronchopulmonary afferent nerves can lead to dyspnea in healthy subjects. A logical extension of the basic research on inflammation and sensory nerve function is that the role of vagal sensory nerve in causing or shaping dyspneic sensations will be exaggerated in those suffering from inflammatory airway disease.

Airway mechanoreceptor deactivation

Airway sensors play an important role in control of breathing. Recently, it was found that pulmonary slowly adapting stretch receptors (SARs) cease after a brief excitation following sodium pump blockade by ouabain. This deactivation can be explained by overexcitation. If this is true, mechanical stimulation of the SARs should also lead to a deactivation. In this study, we recorded unit activity of the SARs in anesthetized, open-chest, and mechanically ventilated rabbits and examined their responses to lung inflation at different constant pressures. Forty-seven of 137 units had a clear deactivation during the lung inflation. The deactivation threshold varied from unit to unit. For a given unit, the higher the inflation pressure, the sooner the deactivation occurs. For example, the SARs deactivated at 3.0 +/- 0.3 and 4.8 +/- 0.4 s when the lungs were inflated to constant pressures of 30 and 20 cmH(2)O, respectively (n = 25, P < 0.0001). The units usually ceased after a brief intense discharge. In some units, their activity shifted to a lower level, indicating a pacemaker switching. Our results support the notion that SARs deactivate due to overexcitation.

Vagal afferent nerves regulating the cough reflex

Coughing is initiated by activation of mechanically and chemically sensitive vagal afferent nerves innervating the airways. All afferent nerve subtypes innervating the airways can modulate the cough reflex. Rapidly adapting and slowly adapting stretch receptors (RARs and SARs, respectively) innervating the intrapulmonary airways and lung may enhance and facilitate coughing. Activation of intrapulmonary C-fibers has been shown to inhibit coughing in anesthetized animals. Extrapulmonary C-fibers and RARs can initiate coughing upon activation. C-fiber-dependent coughing is uniquely sensitive to anesthesia. Tracheal and bronchial C-fibers may also interact with other afferents to enhance coughing. Recent studies in anesthetized guinea pigs have identified a myelinated afferent nerve subtype that can be differentiated from intrapulmonary RARs and SARs and play an essential role in initiating cough. Whether these "cough receptors" are the guinea pig equivalent of the irritant receptors described in the extrapulmonary airways of other species is unclear.

Evidence for a role of neuroepithelial bodies as complex airway sensors: comparison with smooth muscle-associated airway receptors

The epithelium of intrapulmonary airways in many species harbors diffusely spread innervated groups of neuroendocrine cells, called neuroepithelial bodies (NEBs). Data on the location, morphology, and chemical coding of NEBs in mammalian lungs are abundant, but none of the proposed functions has so far been fully established. Besides C-fiber afferents, slowly adapting stretch receptors, and rapidly adapting stretch receptors, recent reviews have added NEBs to the list of presumed sensory receptors in intrapulmonary airways. Physiologically, the innervation of NEBs, however, remains enigmatic. This short overview summarizes our present understanding of the chemical coding and exact location of the receptor end organs of myelinated vagal airway afferents in intrapulmonary airways. The profuse populations that selectively contact complex pulmonary NEB receptors are compared with the much smaller group of smooth muscle-associated airway receptors. The main objective of our contribution was to stimulate the idea that the different populations of myelinated vagal afferents that selectively innervate intraepithelial pulmonary NEBs may represent subpopulations of the extensive group of known electrophysiologically characterized myelinated vagal airway receptors. Future efforts should be directed toward finding out which airway receptor groups are selectively coupled to the complex NEB receptors.

Central pathways of pulmonary and lower airway vagal afferents

Lung sensory receptors with afferent fibers coursing in the vagus nerves are broadly divided into three groups: slowly (SAR) and rapidly (RAR) adapting stretch receptors and bronchopulmonary C fibers. Central terminations of each group are found in largely nonoverlapping regions of the caudal half of the nucleus of the solitary tract (NTS). Second order neurons in the pathways from these receptors innervate neurons located in respiratory-related regions of the medulla, pons, and spinal cord. The relative ease of selective activation of SARs, and to a lesser extent RARs, has allowed for more complete physiological and morphological characterization of the second and higher order neurons in these pathways than for C fibers. A subset of NTS neurons receiving afferent input from SARs (termed pump or P-cells) mediates the Breuer-Hering reflex and inhibits neurons receiving afferent input from RARs. P-cells and second order neurons in the RAR pathway also provide inputs to regions of the ventrolateral medulla involved in control of respiratory motor pattern, i.e., regions containing a predominance of bulbospinal premotor neurons, as well as regions containing respiratory rhythm-generating neurons. Axon collaterals from both P-cells and RAR interneurons, and likely from NTS interneurons in the C-fiber pathway, project to the parabrachial pontine region where they may contribute to plasticity in respiratory control and integration of respiratory control with other systems, including those that provide for voluntary control of breathing, sleep-wake behavior, and emotions.

Physiology of long pranayamic breathing: Neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system

Pranayamic breathing, defined as a manipulation of breath movement, has been shown to contribute to a physiologic response characterized by the presence of decreased oxygen consumption, decreased heart rate, and decreased blood pressure, as well as increased theta wave amplitude in EEG recordings, increased parasympathetic activity accompanied by the experience of alertness and reinvigoration. The mechanism of how pranayamic breathing interacts with the nervous system affecting metabolism and autonomic functions remains to be clearly understood. It is our hypothesis that voluntary slow deep breathing functionally resets the autonomic nervous system through stretch-induced inhibitory signals and hyperpolarization currents propagated through both neural and non-neural tissue which synchronizes neural elements in the heart, lungs, limbic system and cortex. During inspiration, stretching of lung tissue produces inhibitory signals by action of slowly adapting stretch receptors (SARs) and hyperpolarization current by action of fibroblasts. Both inhibitory impulses and hyperpolarization current are known to synchronize neural elements leading to the modulation of the nervous system and decreased metabolic activity indicative of the parasympathetic state. In this paper we propose pranayama's physiologic mechanism through a cellular and systems level perspective, involving both neural and non-neural elements. This theoretical description describes a common physiological mechanism underlying pranayama and elucidate the role of the respiratory and cardiovascular system on modulating the autonomic nervous system. Along with facilitating the design of clinical breathing techniques for the treatment of autonomic nervous system and other disorders, this model will also validate pranayama as a topic requiring more research.

Structure and function relationship in the abdominal stretch receptor organs of the crayfish

The structure/function relationship in the rapidly and slowly adapting stretch receptor organs of the crayfish (Astacus leptodactylus) was investigated using confocal microscopy and neuronal modeling methods. Both receptor muscles were single muscle fibers with structural properties closely related to the function of the receptors. Dendrites of the rapidly adapting neuron terminated in a common pile of nerve endings going in all directions. Dendrites of the slowly adapting neuron terminated in a characteristic T shape in multiple regions of the receptor muscle. The slowly adapting main dendrite, which was on average 2.1 times longer and 21% thinner than the rapidly adapting main dendrite, induced larger voltage attenuation. The somal surface area of the slowly adapting neuron was on average 51% larger than that of the rapidly adapting neuron. Variation in the neuronal geometry was greatest among the slowly adapting neurons. A computational model of a neuron pair demonstrated that the rapidly and the slowly adapting neurons attenuated the dendritic receptor potential like low-pass filters with cut-off frequencies at 100 and 20 Hz, respectively. Recurrent dendrites were observed mostly in the slowly adapting neurons. Voltage signals were calculated to be propagated 23% faster in the rapidly adapting axon, which is 51% thicker than the slowly adapting axon. The present findings support the idea that the morphology of the rapidly and the slowly adapting neurons evolved to optimally sense the dynamic and the static features of the mechanical stimulus, respectively.

Neuroepithelial bodies not connected to pulmonary slowly adapting stretch receptors

Neuroepithelial bodies (NEBs) are believed to be connected with one of the known types of airway receptors. The present studies determined whether NEB afferents are pulmonary slowly adapting stretch receptors (SARs). NEBs are immunoreactive with antibodies against protein gene product (PGP) 9.5 and calcitonin gene-related peptide (CGRP), whereas SARs are reactive with antibody to Na(+)/K(+)-ATPase. Using histochemical staining in combination with confocal microscopy, we compared the morphology of NEBs and SARs in the rat. Our results show that NEBs and SARs are different in location, size, and shape. Double staining of airway tissues for PGP (or CGRP) plus Na(+)/K(+)-ATPase shows that NEBs and SARs do not co-localize. In addition, we electrophysiologically recorded single-unit activity of SARs from the cervical vagus nerve, identified their receptive fields, dissected them into blocks, and then double-stained and examined the receptor structures. We found that the blocks contain the SAR, but not NEB structures. Thus, we conclude that NEBs are not connected to SARs.

Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs.

We have identified the tracheal and laryngeal afferent nerves regulating cough in anaesthetized guinea-pigs. Cough was evoked by electrical or mechanical stimulation of the tracheal or laryngeal mucosa, or by citric acid applied topically to the trachea or larynx. By contrast, neither capsaicin nor bradykinin challenges to the trachea or larynx evoked cough. Bradykinin and histamine administered intravenously also failed to evoke cough. Electrophysiological studies revealed that the majority of capsaicin-sensitive afferent neurones (both Adelta- and C-fibres) innervating the rostral trachea and larynx have their cell bodies in the jugular ganglia and project to the airways via the superior laryngeal nerves. Capsaicin-insensitive afferent neurones with cell bodies in the nodose ganglia projected to the rostral trachea and larynx via the recurrent laryngeal nerves. Severing the recurrent nerves abolished coughing evoked from the trachea and larynx whereas severing the superior laryngeal nerves was without effect on coughing. The data indicate that the tracheal and laryngeal afferent neurones regulating cough are polymodal Adelta-fibres that arise from the nodose ganglia. These afferent neurones are activated by punctate mechanical stimulation and acid but are unresponsive to capsaicin, bradykinin, smooth muscle contraction, longitudinal or transverse stretching of the airways, or distension. Comparing these physiological properties with those of intrapulmonary mechanoreceptors indicates that the afferent neurones mediating cough are quite distinct from the well-defined rapidly and slowly adapting stretch receptors innervating the airways and lungs. We propose that these airway afferent neurones represent a distinct subtype and that their primary function is regulation of the cough reflex.

Bronchopulmonary afferent nerves.

Vagal afferent nerves are the primary communication pathways between the bronchopulmonary system and the central nervous system. Input from airway afferent nerves to the CNS is integrated in the brainstem and ultimately leads to sensations and various reflex outputs. Afferent nerves innervating the airways can be classified into various distinct phenotypes. However, there is no single classification scheme that takes all features, including conduction velocity, cell body diameter, ganglionic origin, and stimuli to which they respond (modality) into account. At present, bronchopulmonary afferent nerves are typically considered to belong to one of three general categories, namely C-fibres, rapidly adapting stretch receptors (RARs), and slowly adapting stretch receptors (SARs). As our understanding of bronchopulmonary afferent nerves continues to deepen, we are likely to see more sophisticated classification schemes emerge. It is clear that the function of afferent fibres can be substantively influenced by airway inflammation and remodelling. The perturbations and perversions of afferent nerve function that occur during these states almost certainly contributes to many of the signs and symptoms of inflammatory airway disease. A more lucid characterization of bronchopulmonary afferent nerves, and a better understanding of the mechanisms by which these nerves influence pulmonary physiology during health and disease anticipates future research.

Postnatal maturation of vagal respiratory reflexes in preterm and full-term lambs.

The postnatal development of ventilatory reflexes originating from bronchopulmonary receptors was assessed in preterm vs. full-term lambs. Ventilation and arterial pressure were repeatedly measured in 10 preterm (gestational age, 132 days) and 7 full-term lambs without sedation from day 1 to day 42. The Hering-Breuer inhibitory reflex (slowly adapting stretch receptors) was assessed by the increase in expiratory time during end-inspiratory occlusion. The pulmonary chemoreflex (C-fiber endings) was assessed by the initial apnea + bradycardia + systemic hypotension and the secondary tachypnea after capsaicin intravenous injection. Results show the following. 1) Premature birth did not modify the maturation of the Hering-Breuer reflex. 2) Whereas a classic pulmonary chemoreflex was observed in the very first hours of life in preterm lambs, the tachypneic component of this reflex was weaker than in full-term lambs on day 1. 3) Premature birth led to a reversed postnatal maturation of this tachypneic response (tendency to increase with postnatal age). Our findings suggest that premature birth in lambs modifies postnatal maturation of the pulmonary chemoreflex.

The K–Cl Cotransporter in the Lobster Stretch Receptor Neurone—A Kinetic Analysis

Experiments were performed to define quantitatively the substrate (K + and Cl −) dependence of the transport function (production of equally large and oppositely directed K +and Cl − flows/currents) of an earlier (Theander et al., 1999) identified electroneutral K–Cl cotransporter in the slowly adapting stretch receptor neurone of the European lobster. The experiments were based on microelectrode techniques. This allowed us to perform steady-state measurements of the so-called “instantaneous” current–voltage relationships (around a holding voltage of −65 mV after a blockage of the cell's action potential and hyperpolarization-activated currents) and intracellular ion concentrations at various settings of the extracellular K + and Cl − concentrations. From the results, we could then define steady-state values of all of the cell's non-KCl cotransporter K + and Cl − currents. Finally, the negative sums of the inferred non-KCl cotransporter K + and Cl − currents could be taken as equivalents of the K–Cl cotransporter's K + and Cl − currents for the reason that, in steady state, all membrane currents add up to zero. For the cotransporter currents, thus inferred for a range from 2.5/410.5 to 40.0/448.0 mM external K +/Cl −, we found that their absolute values increased in a nonlinear fashion from about 5 nA cell −1 at the lowest, to about 20 nA cell −1 at the highest external K +/Cl − concentrations. Formally, this relationship could be reproduced by a Hill function-based enzyme kinetic expression simulating inward and outward transmembrane electroneutral ion transports. Following insertion of this expression into a comprehensive model of electrical membrane functions and intracellular solute and solvent control in the lobster stretch receptor neurone, the model predictions suggested that the K–Cl cotransporter does play an important role in (a) keeping intracellular Cl − low for a proper function of the cell's inhibitory system, and (b) enabling rapid transmembrane K + shifts that provide for a stabilization of the cell's membrane voltage and membrane excitability in cases of varying extracellular K + concentrations. The model predictions gave, however, no clear evidence that the K–Cl cotransporter is critically involved in the cell's volume regulation in conditions of varying extracellular osmolalities.

Response of a pacemaker neuron model to transient pulse trains

AbstractIn this study, the response of the pacemaker neuron model to transient pulse inputs (input sequence composed of a finite number of pulses with interval variations) is examined. The shift of the firing phase of the pacemaker neuron generated by a single pulse stimulus is represented by the phase transition curve. The dynamics of the pacemaker neuron receiving pacemaker pulse stimuli has been analyzed in terms of the one‐dimensional discrete dynamical system derived from the phase transition curve. This paper shows that the dynamics of the model for the transient pulse input can be described by a finite set of phase transition curves. The constructed pacemaker neuron model can reproduce the response of the slowly adapting stretch receptor organ (SAO) of the crayfish to the transient pulse inputs observed in the experiment. It is observed in the experiment that the qualitative property of the response pattern of the SAO to the transient pulse inputs changes suddenly while the input is applied. In order to analyze the generation mechanism underlying the response to the transient pulse inputs, the response of the model is analyzed in detail for inputs with increasing rate, that is, pulse input trains in which the inverse of the input pulse interval monotonically increases. In particular, the mechanism of generation of the paradoxical response, in which the output rate increases monotonously in response to the inhibitory input with increasing rate, is described. © 2002 Scripta Technica, Syst Comp Jpn, 33(3): 63–73, 2002

Characterization of a delayed rectifier potassium channel in the slowly adapting stretch receptor neuron of crayfish

Single channel recordings were performed on enzyme-cleaned slowly adapting sensory neurons of crayfish, in cell-attached configuration, with a physiological K + gradient across the neuronal membrane. An outward rectifying, voltage-gated K + channel with a slope conductance of 13 pS and a K + ion permeability of P K=6.5×10 −14 cm 3/s was characterized. This 13 pS K + channel started to be activated at around 20 mV depolarization. Its open probability increased upon depolarization with V 0.5=−25.3 mV and P max=0.83. The averaged currents showed a delay following the onset of depolarization. The activation time constant was voltage-dependent. The maximal value was 17.0 ms at −25 mV and at +35 mV the time constant was 1.7 ms. Little inactivation was observed throughout the 80- or 1500-ms long depolarization pulses. A sum of two exponentials provided the optimal fit for open time and closed time distribution. At 80-mV depolarization, the open time constants were 0.4 and 10.4 ms; the close time constants were 0.4 and 2.3 ms. The first-latency distribution suggested that at least two closed states preceded two open states. This 13 pS delayed rectifier plays a minor role in the maintenance of the resting membrane potential but contributes to the action potential repolarization. It may also modify the stretch-induced receptor potential and affect the adaptation behaviours in this neuron.

Analysis of models for crustacean stretch receptors.

The mechanisms underlying the diverse responses to step current stimuli of models [Edman et al. (1987) J Physiol (Lond) 384: 649-669] of lobster slowly adapting stretch receptor organs (SAO) and fast-adapting stretch receptor organs (FAO) are analyzed. In response to a step current, the models display three distinct types of firing reflecting the level of adaptation to the stimulation. Low-amplitude currents evoke transient firing containing one to several action potentials before the system stabilizes to a resting state. Conversely, high-amplitude stimulations induce a high frequency transient burst that can last several seconds before the model returns to its quiescent state. In the SAO model, the transition between the two regimes is characterized by a sustained pacemaker firing at an intermediate stimulation amplitude. The FAO model does not exhibit such a maintained firing; rather, the duration of the transient firing increases at first with the stimulus intensity, goes through a maximum and then decreases at larger intensities. Both models comprise seven variables representing the membrane potential, the sodium fast activation, fast inactivation, slow inactivation, the potassium fast activation, slow inactivation gating variables, and the intra cellular sodium concentration. To elucidate the mechanisms of the firing adaptations, the seven-variable model for the lobster stretch receptor neuron is first reduced to a three-dimensional system by regrouping variables with similar time scales. More precisely, we substituted the membrane potential V for the sodium fast activation equivalent potential Vm, the potassium fast inactivation Vn for the sodium fast inactivation Vh, and the sodium slow inactivation Vl for the potassium slow inactivation Vr. Comparison of the responses of the reduced models to those of the original models revealed that the main behaviors of the system were preserved in the reduction process. We classified the different types of responses of the reduced SAO and FAO models to constant current stimulation. We analyzed the transient and stationary responses of the reduced models by constructing bifurcation diagrams representing the qualitatively distinct dynamics of the models and the transitions between them. These revealed that (1) the transient firings prior to reaching the stationary state can be accounted for by the sodium slow inactivation evolving more slowly than the other two variables, so that the changes during the transient firings reflect the bifurcations that the two-dimensional system undergoes when the sodium slow inactivation, considered as a parameter, is varied; and (2) the stationary behaviors of the models are captured by the standard bifurcations of a two-dimensional system formed by the membrane potential and the potassium fast inactivation. We found that each type of firing and the transitions between them is due to the interplay between essentially three variables: two fast ones accounting for the action potential generation and the post-discharge refractoriness, and a third slow one representing the adaptation.

Lung vagal afferent activity in rats with bleomycin-induced lung fibrosis

Bleomycin treatment in rats results in pulmonary fibrosis that is characterized by a rapid shallow breathing pattern, a decrease in quasi-static lung compliance and a blunting of the Hering–Breuer Inflation Reflex. We examined the impulse activity of pulmonary vagal afferents in anesthetized, mechanically ventilated rats with bleomycin-induced lung fibrosis during the ventilator cycle and static lung inflations/deflations and following the injection of capsaicin into the right atrium. Bleomycin enhanced volume sensitivity of slowly adapting stretch receptors (SARs), while it blunted the sensitivity of these receptors to increasing transpulmonary pressure. Bleomycin treatment increased the inspiratory activity, while it decreased the expiratory activity of rapidly adapting stretch receptors (RARs). Pulmonary C-fiber impulse activity did not appear to be affected by bleomycin treatment. We conclude that the fibrosis-related shift in discharge profile and enhanced volume sensitivity of SARs combined with the increased inspiratory activity of RARs contributes to the observed rapid shallow breathing of bleomycin-induced lung fibrosis.

Airway receptors

There are many types of afferent receptor in the airways; at least five in the larynx: pressure, drive, cold, irritant and C-fibre; and at least four in the trachea and bronchi: slowly and rapidly adapting stretch receptors (SARs and RARs), C-fibre receptors, and those in neuroepithelial bodies (NEBs). Histologically enough sensory structures have been identified to account for the various patterns of afferent activity, but most correlations are poor. For the larynx, four or more sensory structures have not definitively been identified with afferent discharges and reflex responses. For the trachea and bronchi, only SARs have been clearly identified morphologically and physiologically. The reflexes and afferent discharges from RARs and C-fibre receptors are fairly clear, some at least of the sensory terminals lie in the epithelium, but receptor complexes have not been mapped out. Nerves in NEBs have been identified, but not their local and central reflex actions.

Measures of complexity in neural spike-trains of the slowly adapting stretch receptor organs

Discrete sequence analysis methods were applied to study spike-trains generated by the isolated neuron of the slowly adapting stretch receptor organ. Calculation of the algorithmic complexity and block entropies of digitized individual spike-train forms allowed us to distinguish different classes of neural behavior. While some spike-trains exhibited significant structure, others displayed diverse degrees of randomness. The sequences recorded during the stimulated portions of the intermittent and walk-through forms, differed considerably from their randomly shuffled surrogates. Informational and grammar complexity measures (in two, four and eight-letter alphabets), tell us things about the structure of spike-trains that are not obtained with conventional spike analysis. Comparison of the conditional entropies for the digitized signals showed that the method distinguishes between different stimulated conditions. Additionally, comparison of the different stimulated conditions with their corresponding surrogates showed that, both, conditional entropies and complexities were significantly different for the two groups. Although the original and the randomly shuffled sequences had the same distribution and average firing rate, their complexity values were different. The results obtained with both measures of sequence structure were quite consistent