Alterations in heat loss and heat production mechanisms in rat exposed to hypergravic fields.
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Biomedical subjects
Publications and source records attributed to J M Horowitz.
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Unrestrained rats were exposed to cold for 1 h during and immediately after exposure to hypergravic fields (1.5--4 G) to determine if they recover their ability to thermoregulate on reentry to 1-G conditions. In contrast to the decreased body temperatures observed when cold exposure occurred concurrently with acceleration, hypothalamic, carotid, and brown fat temperatures did not fall when rats were exposed to cold immediately after return to 1 G. These results support the hypothesis that the thermoregulatory alterations seen under hypergravic conditions are manifestations of an effect of ongoing exposure to hypergravity and can be reversed on termination of acceleration. The reversibility of the thermoregulatory impairment is apparently unaffected by the magnitude of the acceleration field over a range of 1.5--4 G.
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Several cellular events associated with energy turnover in the mitochondria and at the Na+/K+ plasma membrane pump have been formulated in terms of network thermodynamics. The calorigenic role of the Na+/K+ pump is examined in terms of the relationship between the movement of sodium and potassium ions and the chemical reactions involved. In addition, attention is centered on the potential thermogenic role of three mitochondrial pathways involving proton fluxes--namely, one in which protons are transported from the matrix to the intermembrane space; a second in which protons are transferred back into the matrix in conjunction with the synthesis of ATP; and a third wherein protons re-enter the matrix without being coupled to any chemical reaction. (This latter pathway has been delineated by studies on isolated mitochondria and may be unique to brown fat.) At both sites (plasma membrane and mitochondria) the conversion of chemical energy to heat is considered.
Rats exposed to 2g environments (achieved by centrifugation) exhibit a decreased ability to maintain colonic temperature (Tco) when challenged with a 1 hr drop in ambient temperature (Ta). As an extension of this work the present study considers whether the altered ability to maintain Tco is proportional to the magnitude of the acceleration field in the range from 1g-4g, and whether the magnitude of the decreased thermoregulatory ability is related to the onset time of the temperature drop relative to that of the acceleration. Male, Sprague-Dawley rats were instrumented on the experimental day with thermistors for measuring Tco. The unanesthetized rat was then placed in a plexiglas chamber, positioned on a centrifuge 1.37 m in radius, and exposed to 1.5, 2, 2.5, 3, 3.5, or 4g for 5-7 hrs. The exposure to reduced temperature (Ta = approximately 7 degrees C) for 1 hr began 3 hrs after initiation of centrifugation. These experiments indicated that the magnitude of the cold-induced drop in Tco was linearly related to the acceleration field. The effect of a specific stressor (cold) on the thermoregulatory system is therefore a direct function of the gravitational field.
Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.
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Selective dispersion of melanosomes was often observed after iontophoretic injection of cyclic adenosine monophosphate (AMP) from a glass microelectrode positioned in a target melanophore in frog skin (as viewed from above through a microscope), with other melanophores in the field serving as controls. Because the skin has orderly arrays of several types of closely spaced cells, it is probable that at times the microelectrode also impales cells other than melanophores. When cyclic AMP injection inside a cell resulted in dispersion of melanosomes from a perinuclear position into dendritic processes, the onset of dispersion was relatively rapid, in many cases less than 4 min (mean time of onset, 5.3 +/- 2.9 [SD] min). A much slower dispersion (mean time of onset, 19.0 +/- 5.0 min) of melanosomes was observed when the microelectrode was positioned adjacent to a melanophore, and much larger quantities of cyclic AMP were released. In addition, no changes were observed for injections of 5'-AMP or cyclic guanosine monophosphate (GMP) through electrodes positioned inside or adjacent to melanophores. Potential measurements showed that after impaling a clell, a constant transmembrane potential could often be recorded over many minutes, indicating that the membrane tends to seal around the microelectrode. The results indicate that cyclic AMP acts more rapidly on the inside of a cell than when applied outside a cell and allowed to diffuse through the plasma membrane. This study introduces a model system whereby the properties of the plasma membrane and melanocyte-stimulating hormone (MSH) receptors can be studies within a single target cell.
The present study examines the effects of alpha- and beta-adrenergic antagonists (phentolamine and propranolol, respectively) and agonists (phenylephrine, isoproterenol) on the neurally induced temperature changes and membrane potentials of interscapular brown adipocytes. These studies, performed in vivo with anesthetized rats, indicate that both alpha- and beta-adrenergic components are associated with the biphasic temperature changes observed following sympathetic activation of the tissue. Specifically, the initial transient temperature decrease seen after brown fat stimulation appeared to reflect vasoconstriction mediated primarily via alpha-receptors, while the subsequent rise in tissue temperature was associated primarily (though perhaps not entirely) with beta-adrenergic pathways. In contrast, the redistribution of ions across the membrane of the brown adipocyte, a phenomenon manifested as a membrane depolarization, was elicited by phenylephrine (an alpha-agonist) as well as by isoproterenol (a beta-agonist), with the magnitude of the isoproterenol-induced depolarization being comparable to that of the phenylephrine-induced effect.
Upon exposure of rats to 2 G environments (achieved by centrifugation), there occurred a rapid decrease in colonic temperature (Tco) followed, after about 50 min, by a slow recovery toward precentrifugation levels. The initial drop in Tco was accompanied by decreases in hypothalamic and spinal cord temperatures and increases in tail temperature (Tta). In contrast to this anomalous response (i.e., increased heat loss (manifested by increased Tta) despite decreasing temperature at spinal and hypothalamic thermoreceptor areas) the return toward normal Tco appeared to involve appropriate thermoregulatory responses. The initial fall in Tco was decreased in magnitude by inverting the rat during acceleration, thereby suggesting that mechanical forces acting on the brain may underlie this temperature decrease. Exposure to cold during centrifugation allowed further examination of the thermoregulatory system. Unlike the initial acceleration-induced changes, the cold-evoked fall in Tco was not accompanied by increasing Tta and was modified by the environmental conditioning of the rats. These results are consistent with the view that exposure to 2 G adversely affects the thermoregulatory ability of rats challenged by cold.
In the present study, data relevant to the presence or absence of sorting of neural signals were obtained by evaluating the thermal responses to spinal warming in the chronically prepared rat. Specifically, shivering activity and the rate of oxygen consumption (VO2) were measured in unanesthetized rats during cold exposure (10-16 degrees C). Warming the spinal cord at the level of T2 resulted in a significant decrease in shivering (P less than 0.001), without a significant change in VO2. The shivering response was reversed upon cessation of heating. These results are interpreted as indicating a direct influence of spinal cord temperature on shivering but not nonshivering thermogenesis in the rat. Similarly, in previous work with the rat, we have obtained data supporting hypothalamic receptor control of nonshivering but not shivering heat production. These findings are thus consistent with the suggestion that in the rat there occurs a sorting of neural signals. That is, impulses from the three thermoreceptor locations are not integrated in an identical manner for the control of shivering and nonshivering thermogenesis.
Two aspects of the coupling of neural information to brown fat thermogenesis were examined-namely, the thermal responses to increasing neural stimulation and the anatomical nature of the brown fat innervation. Upon stimulation of the nerves to the interscapular brown fat pad, there ensued a biphasic response. This response was manifested by an initial, but transient temperature decrease, followed by a rise in brown fat temperature. The magnitude of both components of this response increased with increasing stimulus strength, thereby demonstrating the ability of the tissue to respond in a graded manner a feature which may underlie the controlled thermogenic response of brown fat observed in the cold-exposed intact animal. No anatomically unique fibre types appeared to be specifically associated with innervation to the brown adipocytes or to the vessels within the fat pad. On the other hand, the nerves entering the interscapular fat pad were morphologically dissimilar, a finding consonent with their functional dissimilarity (i.e., innervation of adipocytes, innervation of blood vessels in the fat pad, and innervation of areas in the overlying skin).
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Four computer models, HM1-HM4, of a particular hippocampal neural network have been developed. The models represent two cell populations, the pyramidal cells and the basket cells; the populations are coupled so that pyramidal cells are inhibited by activity they excite in the basket cell population. In models HM2-HM4, this recurrent inhibitory pathway contains a temporal dispersion element. Models HM3-HM4 place the pyramidal cells in an additional recurrent excitatory feedback loop. HM4 represents a pair of interacting hippocampal networks. Simulated network responses to single-shock stimulation are presented for various parameter values of the four models. Calculations are extended more than one second following stimulation. Particular attention is given to simulation of network instabilities. Simulated neural activity is discussed in view of experimental work on normal (nonepileptogenic) and epileptogenic hippocampal cortex.
Extensive experimental data are available on the neural activity and behavioral correlates of specific networks in the locust and in the cat and rabbit. Two networks were selected for comparison, one involving visual movement detector interneurons in the locust and the second a hippocampal network in mammals. Both networks receive inputs correlated with motor activity. Each network was simulated using CSMP, a Continuous Systems Modeling program developed initially by IBM. Signals along the two simulated networks were calculated when similar inputs were applied. In addition, approaches toward relating behavior to neural activity were compared in the two networks.
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