Review
The Antarctic hemoglobinless icefish, fifty five years later: A unique cardiocirculatory interplay of disaptation and phenotypic plasticity

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Abstract

The teleostean Channichthyidae (icefish), endemic stenotherms of the Antarctic waters, perennially at or near freezing, represent a unique example of disaptation among adult vertebrates for their loss of functional traits, particularly hemoglobin (Hb) and, in some species, cardiac myoglobin (Mb), once considered to be essential-life oxygen-binding chromoproteins. Conceivably, this stably frigid, oxygen-rich habitat has permitted high tolerance of disaptation, followed by subsequent adaptive recovery based on gene expression reprogramming and compensatory responses, including an alternative cardio-circulatory design, Hb-free blood and Mb-free cardiac muscle. This review revisits the functional significance of the multilevel cardio-circulatory compensations (hypervolemia, near-zero hematocrit and low blood viscosity, large bore capillaries, increased vascularity with great capacitance, cardiomegaly with very large cardiac output, high blood flow with low systemic pressure and systemic resistance) that counteract the challenge of hypoxemic hypoxia by increasing peripheral oxygen transcellular movement for aerobic tissues, including the myocardium. Reconsidered in the context of recent knowledge on both polar cold adaptation and the new questions related to the advent of nitric oxide (NO) biology, these compensations can be interpreted either according to the “loss-without-penalty” alternative, or in the context of an excessive environmental oxygen supply at low cellular cost and oxygen requirement in the cold. Therefore, rather than reflecting oxygen limitation, several traits may indicate structural overcompensation of oxygen supply reductions at cell/tissue levels. At the multilevel cardio-circulatory adjustments, NO is revealing itself as a major integrator, compensating disaptation with functional phenotypic plasticity, as illustrated by the heart paradigm. Beside NOS-dependent NO generation, recent knowledge concerning Hb/Mb interplay with NO and nitrite has revealed unexpected functions in addition to the classical respiratory role of these proteins. In fact, nitrite, a major biologic reservoir of NO, generates it through deohyHb- and deoxyMb-dependent nitrite reduction, thereby regulating hypoxic vasodilation, cellular respiration and signalling. We suggest that both Hb and Mb are involved as nitrite reductases under hypoxic conditions in a number of cardiocirculatory processes. On the whole, this opens new horizons in environmental and evolutionary physiology.

Introduction

Fifty five years have elapsed since the Channichthyidae, named icefish by early British whalers for their ghostly white appearance and their nearly transparent blood (blodlaus-fisk), were first described physiologically by Ruud (1954) in its seminal Nature paper. These stenotherm teleosts, endemic inhabitants of the frigid Antarctic waters, provide an unique example of disaptation among adult vertebrates for their loss of respiratory pigments hemoglobin (Hb) and, in some species, cardiac myoglobin (Mb). The development of their alternative physiological design, Hb-free blood and Mb-free muscle cells capable to function similarly well in the cold Antarctic habitat, represents a treasure house for scientists concerned with evolutionary and environmental physiology. The central goal of this review is to revisit the icefish cardio-circulatory function in the context of both the recent knowledge on polar cold adaptation and the new broad questions related to the adaptive significance of these fascinating animals. We will update the specialized adjustments and maladaptive phenotype characteristics of this animal in light of new findings on both the multilevel (from molecular to organ and system) cardio-circulatory compensations to the lack of the respiratory pigments, and the interplay between plasticity and vulnerability of the heart. Moreover, using new data from our recent studies on cardiac nitric oxide synthase (NOS)/nitric oxide (NO) system in Antarctic fishes, its important emerging role in modulating these cardio-circulatory adjustments will be discussed. In conclusion, the icefish can be proposed as a “case study” ideally suited for important insights into the understanding of factors that set limits on the evolution of phenotypes, morphologic novelties and adaptations; at the same time, it provides some lessons which are of relevance for environmental cardiac biology in vertebrates. However, before addressing this issue, it is useful for the non-expert reader to summarize briefly our present knowledge about thermal adaptation and cold tolerance, which furnishes the premise for understanding icefish biology.

Section snippets

Thermal tolerance in fish

Temperature is a major limiting factor in a wide spectrum of physiological processes. However, organisms have evolved compensatory adaptation, resulting from either short-term acclimatory mechanisms (acclimatization) that lie within the genetic repertoire of an individual; or long-term changes (evolutionary adaptation) resulting from the action of natural selection (Hazel, 1995, Hochachka and Somero, 2002, Pörtner et al., 2007). Both these changes are integrated at the whole organism level to

The notothenioid cold-adaptive radiation

Twice the size of Australia, Antarctica is isolated from other continents by two large bodies of water, the Ross and Weddell seas. After the breakup of Gondwana at the Oligocene/Miocene boundary 25 Mya, Antarctica underwent a long period of climatic cooling caused by the opening of the Drake Passage and formation of the Antarctic Polar Front (APF), which persists to the present (Eastman, 1993). APF functions as a cold “wall” that prevents mixing of the waters of the Southern Ocean with those of

The hemoglobinless icefish as an unique example of disaptation

It has been suggested that the Antarctic habitat, for both its stably frigid, well oxygenated waters and the low competition, in comparison with other fish flocks of other habitats, has permitted a higher tolerance of evolutionary loss of function (disaptation, according to the nomenclature of Baum and Larson, 1991), which may be followed by subsequent adaptive recovery (Clarke and Johnston, 1996, Johnston et al., 2003, Sidell and O'Brien, 2006, Cheng and Detrich, 2007). Examples of disaptation

Compensatory adjustments in the icefish

Although the mechanistic nature of the intertissue coordinating process remains still hypothethical in the icefish, the major compensatory changes to Hb and Mb losses appear orchestrated by a number of homeostatic loops activated at different levels to ensure an efficient transcellular movement of oxygen from capillaries to mitochondria, so that the channichtyid redox biome is appropriately maintained, thus avoiding the risk of hypoxemic and intracellular hypoxia. In the last twenty years a

Circulatory adjustments

In the hemoglobinless blood, oxygen is carried strictly in physical solution. Being oxygen solubility higher at low temperature, the arterial oxygen-carrying capacity in the icefish is < 9 to 10% of that seen in closely related red-blooded species (Ruud, 1954, Holeton, 1970). A major compensation consists in an impressive increase of mass-specific blood volume which is 2–4 times greater than in red-blooded teleosts (C. aceratus: Holeton, 1970, Hemmingsen and Douglas, 1970; Chionodraco hamatus:

Vascular adjustments

The major determinants of intracellular pO2 are the capillary supply and the intracellular diffusion distance. As mentioned above, a striking notothenioid feature is the very large diameter fibres of the skeletal musculature which, being common to both the Antarctic endemic and the sub-Antarctic species living at much higher temperature (Beagle Channel), may hence represent a phyletic trait (Johnston et al., 2003). Since the consequent longer diffusional distances (see below) accentuate the

The heart as a major factor in the icefish compensation

In comparison to (Hb+) species, the icefish heart, to ensure adequate oxygen delivery to the aerobic tissues, has dramatically increased its cardiac output (CO, i.e. the product of stroke volume and heart rate) with consequent elevation in the rate of blood flow through the vasculature, thereby maximizing the driving pO2 gradient across the length of the exchange area. That is, it moves a very large blood volume through a high flow/low pressure/low resistance vascular circuit. To cope with this

NO as a major breakthrough in cardio-circulatory and redox biome homeostasis

After its discovery as a major cardioactive and vasodilator principle, marked by a Nobel prize award twenty years ago, the NOS/NO system has been recognized as one of the oldest universal inter- and intra-cellular messengers of both prokaryotes and eukaryotes, able to integrate cell biochemistry and energetics. NO synthesis is achieved through several enzymatic pathways (NOS-dependent NO generation from the guanidino group of L-arginine), as well as nonenzymatic processes, which can coexist

Open questions and perspectives

The processes leading to the evolutionary adaptation of a new phenotype to changing environments include complex, often subtle changes in multiple traits that, integrated at the whole organism level, must obey to governance mechanisms for physiological systems, according to self-organization principles. This implies that the rules governing the behaviour of an emergent system, as in our case the new channichthyid phenotype, are fundamentally different and independent from the rules governing

Acknowledgements

Bruno Tota is particularly indebted to his friend and colleague Prof. I. A. Johnston, who, in the far August 1980, during a visit to his lab in St. Andrews, for the first time, by showing an icefish specimen with its enigmatically white large heart, paved the way to the still ongoing studies of our lab on this wonderful animal. We are also grateful to Prof. Bruce Sidell for his friendly cooperation and support at Palmer Station, Antarctica.

This work was supported by PNRA (Programma Nazionale di

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