William K. Milsom

Peripheral arterial chemoreceptors and the evolution of the carotid body.

There has been a reduction in the distribution of peripheral respiratory O(2) chemoreceptors from multiple, dispersed sites in fish and amphibia to a single dominant receptor site in birds and mammals. In the process, the cells in the fish gill associated with O(2) chemosensing (5-HT containing neuroepithelial cells often found in association with ACh/catecholamine (CA) containing cells) are replaced by the glomus cells of the mammalian carotid body (which contain multiple putative neurotransmitter substances, including 5-HT, CA and ACh, all within the same cells), although this difference may be more superficial than first appears. While still highly speculative, these trends would appear to be correlated with the transition from aquatic respiration and bimodal breathing, and from animals with intra-cardiac shunts (two situations where the ability to sense O(2) at multiple sites would be an advantage), to strictly air breathing in animals with no intra-cardiac shunts. It is also tempting to speculate that while the basic O(2)-sensing mechanism is the same for all receptor cells, the receptor groups in fish have evolved in such a way to make the responses of some more sensitive to changes in O(2) delivery than others. The net result is that those receptors associated with the first gill arch of fish (the third branchial arch) become the carotid body in higher vertebrates associated with the regulation of ventilation and ensuring oxygen supply to the gas exchange surface. Those receptors associated with the second gill arch (fourth branchial arch) become the aortic bodies capable of sensing changes in oxygen content of the blood and primarily involved in regulating oxygen transport capacity through erythropoiesis and changes in blood volume.

Molecular Evolution of Cytochrome c Oxidase Underlies High-Altitude Adaptation in the Bar-Headed Goose

Bar-headed geese (Anser indicus) fly at up to 9,000 m elevation during their migration over the Himalayas, sustaining high metabolic rates in the severe hypoxia at these altitudes. We investigated the evolution of cardiac energy metabolism and O(2) transport in this species to better understand the molecular and physiological mechanisms of high-altitude adaptation. Compared with low-altitude geese (pink-footed geese and barnacle geese), bar-headed geese had larger lungs and higher capillary densities in the left ventricle of the heart, both of which should improve O(2) diffusion during hypoxia. Although myoglobin abundance and the activities of many metabolic enzymes (carnitine palmitoyltransferase, citrate synthase, 3-hydroxyacyl-coA dehydrogenase, lactate dehydrogenase, and pyruvate kinase) showed only minor variation between species, bar-headed geese had a striking alteration in the kinetics of cytochrome c oxidase (COX), the heteromeric enzyme that catalyzes O(2) reduction in oxidative phosphorylation. This was reflected by a lower maximum catalytic activity and a higher affinity for reduced cytochrome c. There were small differences between species in messenger RNA and protein expression of COX subunits 3 and 4, but these were inconsistent with the divergence in enzyme kinetics. However, the COX3 gene of bar-headed geese contained a nonsynonymous substitution at a site that is otherwise conserved across vertebrates and resulted in a major functional change of amino acid class (Trp-116 → Arg). This mutation was predicted by structural modeling to alter the interaction between COX3 and COX1. Adaptations in mitochondrial enzyme kinetics and O(2) transport capacity may therefore contribute to the exceptional ability of bar-headed geese to fly high.

Pontine influences on breathing: an overview.

Historical and contemporary views of the functional organization of the lateral pontine regions influencing breathing are reviewed. In vertebrates, the rhombencephalon generates a breathing rhythm and detailed motor pattern that persist throughout life. Key to this process is an essentially continuous column of neurons extending from the spino-medullary border through the ventrolateral medulla, continuing through the ventral pons and arcing into the dorsolateral medulla. Comparative neuroanatomy and physiology indicate this is a richly interconnected network divided into serial, functionally distinct compartments. Serial compartmentalization of pontomedullary structures related to breathing also reflects the developmental segmentation of the rhombencephalon. However, with migration of cell groups such as the facial nucleus from the pons to the medulla during ontogeny, the boundaries of the adult pons are sometimes difficult to precisely define. Accordingly, a working definition of rostral and caudal pontine boundaries for adult mammals is depicted.

7 Afferent Inputs Associated with Cardioventilatory Control in Fish

Publisher Summary This chapter describes the afferent inputs associated with cardioventilatory control in fish. The basic respiratory rhythm and rhythmic contractions of the heart result from the actions of endogenous rhythm generators and do not require afferent feedback for their initiation or maintenance in fish. Mechanoreceptors sensitive to displacement of the pharynx, pharyngeal pads, gill arches, gill rakers and filaments, and air-breathing organs have been identified in fishes. As in other vertebrates, these mechanoreceptors appear to be simple free nerve endings located in connective tissue or muscle. There is direct and indirect evidence that indicates that some fishes may possess intracardiac receptors homologous to mammalian atrial and ventricular stretch receptors. The internally oriented chemoreceptors respond to the mixed venous blood somewhere between the ventral aorta and the afferent filamental artery. Nociceptors with characteristics similar to juxtapulmonary receptors in mammalian lungs have been demonstrated in the gills of dogfish.

Cardiovascular and respiratory reflexes in the tropical fish, traira (Hoplias malabaricus): CO2/pH chemoresponses

To examine the distribution and physiological role of CO2/pH-sensitive chemoreceptors in the gills of the tropical fish, traira (Hoplias malabaricus), fish were exposed to acute environmental hypercarbia (1.25, 2.5 and 5.0% CO2 in air) and subjected to injections of HCl into the ventral aorta and buccal cavity. This was done before and after selective denervation of branchial branches of the IXth and Xth cranial nerves to various gills arches. Hypercarbia produced a significant decrease in heart rate, a mild hypotension as well as increases in both ventilation rate and ventilation amplitude. The data suggest that the hypercarbic bradycardia and increase in ventilation frequency arise from receptors exclusively within the gills but present on more than the first gill arch, while extra-branchial receptors may also be involved in controlling the increase in ventilation amplitude. With the exception of a decrease in heart rate in response to HCl injected into the ventral aorta, the acid injections (internal and external) did not mimic the cardiorespiratory responses observed during hypercarbia suggesting that changes in CO2 are more important than changes in pH in producing cardiorespiratory responses. Finally, the data indicate that chemoreceptors sensitive to CO2/pH and to O2 in the gills of this species involved in producing ventilatory responses are distributed in a similar fashion, but that those involved in producing the bradycardia are not.

Sensory receptors in the first gill arch of rainbow trout

Afferent neural activity was recorded from sensory receptors innervated by the glossopharyngeal nerve (cranial nerve IX) in isolated, perfused first gill arch preparations from rainbow trout. The present study demonstrates the presence of every major type of peripheral cardio-respiratory receptor described in fish in this preparation. Oxygen-sensitive chemoreceptors responsive to internal and/or external hypoxia and cyanide were present. Qualitatively these receptors behaved in an identical fashion which was also similar to that described for mammalian carotid body chemoreceptors. About 5% of the sensory receptors examined were O2-sensitive. proprioceptors were the most numerous receptor type identified and were sensitive to mechanical stimulation of the arch, rakers or filaments. Finally, baroreceptors, the least numerous class of receptor identified, were also present with activity that was altered in response to changes in perfusion pressure. While the reflex responses elicited by the stimulation of these receptors were not addressed in this study, it is likely that these receptors contribute to the reflex cardio-respiratory responses to changes in gill perfusion, gill deflection and hypoxia (environmental or internal) described in fishes. These data thus support suggestions concerning homologies between the first gill arch of teleosts and the carotid bodies of mammals and the importance of the first gill arch in trout in cardio-respiratory control.

Regulation of cardiac rhythm in hibernating mammals

The dramatic fall in heart rate exhibited by mammals entering hibernation begins before there is any noticeable fall in body temperature. The initial, progressive decrease in heart rate is the result of a cyclic parasympathetic activation that induces skipped beats and regular asystoles as well as slows the even heart beat. As body temperature subsequently falls, the parasympathetic influence is progressively withdrawn and periods of parasympathetic and sympathetic dominance alternate and give rise to regular periods of arrhythmia (tachycardia followed by bradycardia), and occasional long asystoles or periods of highly irregular cardiac activity. Superimposed on this is a vagally-mediated, respiratory sinus arrhythmia that is accentuated in species that breathe episodically. These events give way to a uniform heart rate in deep hibernation at low temperatures where both parasympathetic and sympathetic tone appear absent. The complete absence of tone is not a function of reduced temperature but is reflective of the state of deep, steady state hibernation. The elevation in heart rate that accompanies the onset of arousal is the result of dramatic increases in sympathetic activation that precede any increases in body temperature. As body temperature then rises, sympathetic influence is slowly withdrawn. Arrhythmias are also common during natural arousals or shifts from lower to warmer hibernation temperatures as periods of parasympathetic and sympathetic dominance again alternate en route to re-establishing a steady state in euthermia. The mechanism behind, and the biological significance of, cardiac changes mediated through orchestrated arrhythmias remain unknown.

Phylogeny of CO2/H+ chemoreception in vertebrates

The traditional view has been that respiratory chemoreceptors responsive to changes in P(CO(2))/pH first evolved in air breathing vertebrates at both peripheral and central sites. Recent evidence, however, suggests that fish also possess chemoreceptors responsive to changes in P(CO(2)) per se. In many species these receptors reside in the gills and respond primarily to changes in aquatic rather than arterial P(CO(2)). There is also scattered evidence to suggest that central CO(2)/H(+)-sensitive chemoreceptors may be present in representatives of all fish groups but only the data for air breathing fish are strong and convincing. The phylogenetic trends that are emerging indicate that the use of CO(2) chemoreception for cardiorespiratory processes arose much earlier than previously believed, (arguably) that CO(2) chemoreception may first have arisen in the periphery sensitive to the external environment and that central CO(2)/H(+) chemoreception subsequently arose multiple times in association with several of the independent origins of air breathing, and that the mechanisms of CO(2)/H(+) chemotransduction may be as varied as the different receptor groups involved.

The trans-Himalayan flights of bar-headed geese (Anser indicus)

Birds that fly over mountain barriers must be capable of meeting the increased energetic cost of climbing in low-density air, even though less oxygen may be available to support their metabolism. This challenge is magnified by the reduction in maximum sustained climbing rates in large birds. Bar-headed geese (Anser indicus) make one of the highest and most iconic transmountain migrations in the world. We show that those populations of geese that winter at sea level in India are capable of passing over the Himalayas in 1 d, typically climbing between 4,000 and 6,000 m in 7–8 h. Surprisingly, these birds do not rely on the assistance of upslope tailwinds that usually occur during the day and can support minimum climb rates of 0.8–2.2 km·h−1, even in the relative stillness of the night. They appear to strategically avoid higher speed winds during the afternoon, thus maximizing safety and control during flight. It would seem, therefore, that bar-headed geese are capable of sustained climbing flight over the passes of the Himalaya under their own aerobic power.

Oxygen sensitive afferent information arising from the first gill arch of yellowfin tuna

Single nerve fiber discharge was recorded from O2 sensitive receptors in the first gill arch of the yellowfin tuna, Thunnus albacares, in vitro. These receptors were innervated by the vagus nerve and increased their discharge in response to decreasing perfusion rate, decreasing perfusion PO2 and, in most fibers, to decreasing external PO2. Fibers responding to environmental hypoxia exhibited an exponential increase in discharge to decreasing external PO2 with a sensitivity similar to that exhibited by cat carotid body chemoreceptors. Indirect evidence suggests that these receptors are located near the gill vasculature and are more sensitive to changes in arterial PO2 than water PO2. Their response characteristics and hypoxic sensitivity strongly implicate them as the afferent limb in the cardiac responses and perhaps also the ventilatory responses exhibited by tuna to environmental hypoxia.