Dependence of Myocardial Hypothermia Tolerance on Sources of Activator Calcium

Wang, Shi Qiang; Huang, Yi-Hua; Liu, Kesheng; Zhou, Zixin

doi:10.1006/cryo.1997.2040

Cited by 35 publications

(26 citation statements)

References 27 publications

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“…An upregulation of the gene expression of SERCA and reduced levels of phospholamban expression were also found in hearts of hibernating ground squirrels (8). Together, these adjustments lead to much faster rates of reuptake of Ca 2ϩ into the SR, which explains why myocytes in hibernators at low body temperature have significantly faster relaxation rates than in hypothermic nonhibernators (80). Similar adjustments apparently also occur in daily heterotherms.…”

Section: Serca and The Hibernating Heartmentioning

confidence: 83%

Effects of polyunsaturated fatty acids on hibernation and torpor: a review and hypothesis

Ruf¹,

Arnold²

2008

American Journal of Physiology-Regulatory, Integrative and Comp

140

134

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Polyunsaturated fatty acids (PUFAs) can have strong effects on hibernation and daily torpor in mammals. High dietary PUFA contents were found to increase proneness for torpor, decrease body temperatures, prolong torpor bout duration, and attenuate hibernation mass loss. The mechanism by which PUFAs enhance torpor and hibernation is unknown, however. On the basis of a review of the literature, and on reexamining our own data on alpine marmots, we propose that effects on hibernation are not due to PUFAs in general, but to shifts in the ratio of n-6 PUFAs to n-3 PUFAs in membrane phospholipids. Specifically, high ratios of n-6 to n-3 PUFAs increase the activity of the Ca2+-Mg2+ pump in the sarcoplasmic reticulum of the heart (SERCA) and counteract Q10 effects on SERCA activity at low tissue temperatures. Therefore, high n-6 to n-3 PUFA ratios in cardiac myocyte membranes appear to protect the hibernating heart from arrhythmia, which in hypothermic nonhibernators is caused by massive increases in cytosolic Ca2+. The resulting reduced risk of cardiac arrest during hypothermia may explain why increased dietary uptake of n-6 PUFAs, but not of n-3 PUFAs, can strongly enhance the propensity for hibernation, and allows heterotherms to reach lower body temperatures, with associated increased energy savings. Therefore, at least for herbivorous hibernators, such as marmots, linoleic acid (C18:2 n-6)--the dietary source of all n-6 PUFAs--appears to represent a crucial and limited resource in natural environments.

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Section: Serca and The Hibernating Heartmentioning

confidence: 83%

Effects of polyunsaturated fatty acids on hibernation and torpor: a review and hypothesis

Ruf¹,

Arnold²

2008

American Journal of Physiology-Regulatory, Integrative and Comp

140

134

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“…Modified DPI-ELISA absorbance readings were corrected by subtraction of negative controls containing no protein, and values were expressed relative to 37°C for both EC and LT. Data in panel (a) and (b) were analyzed using a one-way analysis of variance with a post hoc Tukey's test (p < 0.05), for each parameter measured, and the data in panel (c) were analyzed using a paired T test (p < 0.05). Values that are not statistically different from each other share the same letter notation transients following excitation is actually increased following excitation at low temperatures, and as a result, stronger contractions with higher amplitudes are seen at lower temperatures (Wang et al 1997(Wang et al , 2000Liu et al 1990Liu et al , 1993. Therefore, greater spikes in intracellular [Ca 2+ ] following an action potential may lead to an activation of NFAT-calcineurin pathway, thus allowing for a maintenance of muscle mass during hibernation.…”

Section: Discussionmentioning

confidence: 99%

“…For example, NFATc3 is known to regulate targets like myoferlin that are important for muscle preservation during torpor (Zhang and Storey 2015;Demonbreun et al 2010). As a result, NFATc3 binding to DNA was not decreased by Ca 2+ to the same extent as NFATc1 after increases in intracellular [Ca 2+ ] were observed from the sharp Ca 2+ transients seen at lower temperatures during torpor (Wang et al 1997(Wang et al , 2000Liu et al 1990Liu et al , 1993. Due to the specificity of intranuclear Ca 2+ on NFAT-DNA binding during torpor, this effect is likely not due to the binding and blocking of DNA by intranuclear Ca 2+ (Dobi and Agoston 1998).…”

Section: Discussionmentioning

confidence: 99%

Regulation of gene expression by NFAT transcription factors in hibernating ground squirrels is dependent on the cellular environment

Zhang

2016

Cell Stress and Chaperones

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Calcineurin is a calmodulin-stimulated phosphatase that regulates the nuclear translocation of nuclear factor of activated T cell (NFAT) c1-4 through dephosphorylation. We believe that this mechanism plays various roles in the remodeling and maintenance of Ictidomys tridecemlineatus skeletal muscle. During hibernation, bouts of torpor and arousal take place, and squirrels do not lose muscle mass despite being inactive. Protein expression of Ca 2+ signaling proteins were studied using immunoblotting. A DNA-protein interaction ELISA technique was created to test the binding of NFATs in the nucleus to DNA probes containing the NFAT response element under environmental conditions reflective of those during hibernation. Calcineurin protein levels increased by 3.08-fold during torpor (compared to euthermic control), whereas calpain1 levels also rose by 3.66-fold during torpor. Calmodulin levels were elevated upon entering torpor. NFATc4 binding to DNA showed a 1.4-fold increase during torpor, and we found that this binding was further enhanced when 600 nM of Ca 2+ was supplemented. We also found that decreasing the temperature of ELISAs resulted in progressive decreases in the binding of NFATs c1, c3, and c4 to DNA. In summary, calmodulin and calpain1 appear to activate calcineurin and NFATc4 during torpor. NFAT binding to target promoters is affected by intranuclear [Ca 2+ ] and environmental temperatures. Therefore, Ca 2+ signaling and temperature changes play key roles in regulation of the NFAT-calcineurin pathway in skeletal muscle of hibernating 13-lined ground squirrels over the torpor-arousal cycle, and they may contribute to the avoidance of disuse-induced muscle atrophy that occurs naturally in these animals.

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“…Much of this resistance has been attributed to the hibernators' ability to maintain Ca 2ϩ balance (Ref. 92 and references therein). L-type Ca 2ϩ channels of nonhibernators and hibernators have similar characteristics, and thus sarcoplasmic reticulum function is a more likely mechanism for the maintenance of Ca 2ϩ balance (46).…”

mentioning

confidence: 99%

Invited Review: Molecular adaptations in mammalian hibernators: unique adaptations or generalized responses?

Breukelen

Martin

2002

Journal of Applied Physiology

115

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are unique among mammals in their ability to attain, withstand, and reverse low body temperatures. Hibernators repeatedly cycle between body temperatures near zero during torpor and 37°C during euthermy. How do these mammals maintain cardiac function, cell integrity, blood fluidity, and energetic balance during their prolonged periods at low body temperature and avoid damage when they rewarm? Hibernation is often considered an example of a unique adaptation for low-temperature function in mammals. Although such adaptation is apparent at the level of whole animal physiology, it is surprisingly difficult to demonstrate clear examples of adaptations at the cellular and biochemical levels that improve function in the cold and are unique to hibernators. Instead of adaptation for improved function in the cold, the key molecular adaptations of hibernation may be to exploit the cold to depress most aspects of biochemical function and then rewarm without damage to restore optimal function of all systems. These capabilities are likely due to novel regulation of biochemical pathways shared by all mammals, including humans. torpor; hypothermia; differential gene expression WHEN A HUMAN IS EXPOSED TO low environmental temperatures and body temperature begins to fall, hypothermia ensues: the shivering response fails at a body temperature of 30-32°C, the heart fibrillates at 27-29°C, and ventilation ceases at 23-27°C, leading to death (reviewed in Refs. 47 and 48). However, a myriad of mammals avoid the damage associated with hypothermia by evoking controlled excursions to reduced body temperatures called torpor. In contrast to hypothermia, the reduction of body temperature in hibernators is not a patholological state (56). Deep hibernators are the masters of this adaptive hypothermia because they can maintain body temperatures below 0°C for up to 3 wk (2, 26, 34). Key characteristics of torpor include a profound reduction of metabolism (up to 1/100th of basal metabolic rate), reduced heart rate, and extremely low body temperature (reviewed in Ref. 90). The physiological consequences associated with hibernation provide a natural model for the study of ischemia, muscle and bone disuse atrophy, hypothermia, ketosis, organ transplant therapy, obesity, kidney failure, and cardiac arrhythmogenesis (e.g., Refs. 18,28,70,93,95).Ground-dwelling sciurid rodents have become the favorite model organisms for recent laboratory studies to explore the molecular bases of mammalian hibernation. In nature, these species exhibit a strict circannual rhythm of reproduction, fattening, and hibernation (for review, see Ref. 49). The cycle begins in the spring with mating, gestation, and birth. The seasons' young are

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Dependence of Myocardial Hypothermia Tolerance on Sources of Activator Calcium

Cited by 35 publications

References 27 publications

Effects of polyunsaturated fatty acids on hibernation and torpor: a review and hypothesis

Effects of polyunsaturated fatty acids on hibernation and torpor: a review and hypothesis

Regulation of gene expression by NFAT transcription factors in hibernating ground squirrels is dependent on the cellular environment

Invited Review: Molecular adaptations in mammalian hibernators: unique adaptations or generalized responses?

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