Selected Contribution: Improved anoxic tolerance in rat diaphragm following intermittent hypoxia

2001 ◽  
Vol 90 (6) ◽  
pp. 2508-2513 ◽  
Author(s):  
Thomas L. Clanton ◽  
Valerie P. Wright ◽  
Peter J. Reiser ◽  
Paul F. Klawitter ◽  
Nanduri R. Prabhakar
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Intermittent Hypoxia ◽  
Contractile Function ◽  
Myosin Heavy Chain Isoforms ◽  
Adaptive Responses ◽  
Low Frequencies ◽  
Myosin Heavy Chain Isoform ◽  
Obstructive Sleep

Intermittent hypoxia (IH), associated with obstructive sleep apnea, initiates adaptive physiological responses in a variety of organs. Little is known about its influence on diaphragm. IH was simulated by exposing rats to alternating 15-s cycles of 5% O2 and 21% O2 for 5 min, 9 sets/h, 8 h/day, for 10 days. Controls did not experience IH. Diaphragms were excised 20–36 h after IH. Diaphragm bundles were studied in vitro or analyzed for myosin heavy chain isoform composition. No differences in maximum tetanic stress were observed between groups. However, peak twitch stress ( P < 0.005), twitch half-relaxation time ( P < 0.02), and tetanic stress at 20 or 30 Hz ( P < 0.05) were elevated in IH. No differences in expression of myosin heavy chain isoforms or susceptibility to fatigue were seen. Contractile function after 30 min of anoxia (95% N2-5% CO2) was markedly preserved at all stimulation frequencies during IH and at low frequencies after 15 min of reoxygenation. Anoxia-induced increases in passive muscle force were eliminated in the IH animals ( P < 0.01). These results demonstrate that IH induces adaptive responses in the diaphragm that preserve its function in anoxia.

Single-fiber myosin heavy chain polymorphism: how many patterns and what proportions?

2003 ◽  
Vol 285 (3) ◽  
pp. R570-R580 ◽  
Author(s):  
Vincent J. Caiozzo ◽  
Michael J. Baker ◽  
Karen Huang ◽  
Harvey Chou ◽  
Ya Zhen Wu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Muscle Fibers ◽  
Myosin Heavy Chain Isoforms ◽  
Single Fiber ◽  
Myosin Heavy Chain Isoform ◽  
Skeletal Muscle Fibers ◽  
Velocity Relationship ◽  
Force Velocity

Previous studies have reported the existence of skeletal muscle fibers that coexpress multiple myosin heavy chain isoforms. These surveys have usually been limited to studying the polymorphic profiles of skeletal muscle fibers from a limited number of muscles (i.e., usually <4). Additionally, few studies have considered the functional implications of polymorphism. Hence, the primary objective of this study was to survey a relatively large number of rat skeletal muscle/muscle regions and muscle fibers ( n≈ 5,000) to test the hypothesis that polymorphic fibers represent a larger fraction of the total pool of fibers than do so-called monomorphic fibers, which express only one myosin heavy chain isoform. Additionally, we used Hill's statistical model of the force-velocity relationship to differentiate the functional consequences of single-fiber myosin heavy chain isoform distributions found in these muscles. The results demonstrate that most muscles and regions of rodent skeletal muscles contain large proportions of polymorphic fibers, with the exception of muscles such as the slow soleus muscle and white regions of fast muscles. Several muscles were also found to have polymorphic profiles that are not consistent with the I↔IIA↔IIX↔IIB scheme of muscle plasticity. For instance, it was found that the diaphragm muscle normally contains I/IIX fibers. Functionally, the high degree of polymorphism may 1) represent a strategy for producing a spectrum of contractile properties that far exceeds that simply defined by the presence of four myosin heavy chain isoforms and 2) result in relatively small differences in function as defined by the force-velocity relationship.

scholarly journals Regulatory light chain phosphorylation augments length-dependent contraction in PTU-treated rats

2018 ◽  
Vol 151 (1) ◽  
pp. 66-76 ◽  
Author(s):  
Jason J. Breithaupt ◽  
Hannah C. Pulcastro ◽  
Peter O. Awinda ◽  
David C. DeWitt ◽  
Bertrand C.W. Tanner
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Light Chain ◽  
Myosin Heavy Chain Isoforms ◽  
Regulatory Light Chain ◽  
Cardiac Myosin ◽  
Myosin Heavy Chain Isoform ◽  
Cross Bridge ◽  
Detachment Rate ◽  
Length Dependent Activation

Force production by actin–myosin cross-bridges in cardiac muscle is regulated by thin-filament proteins and sarcomere length (SL) throughout the heartbeat. Prior work has shown that myosin regulatory light chain (RLC), which binds to the neck of myosin heavy chain, increases cardiac contractility when phosphorylated. We recently showed that cross-bridge kinetics slow with increasing SLs, and that RLC phosphorylation amplifies this effect, using skinned rat myocardial strips predominantly composed of the faster α-cardiac myosin heavy chain isoform. In the present study, to assess how RLC phosphorylation influences length-dependent myosin function as myosin motor speed varies, we used a propylthiouracil (PTU) diet to induce &gt;95% expression of the slower β-myosin heavy chain isoform in rat cardiac ventricles. We measured the effect of RLC phosphorylation on Ca2+-activated isometric contraction and myosin cross-bridge kinetics (via stochastic length perturbation analysis) in skinned rat papillary muscle strips at 1.9- and 2.2-µm SL. Maximum tension and Ca2+ sensitivity increased with SL, and RLC phosphorylation augmented this response at 2.2-µm SL. Subtle increases in viscoelastic myocardial stiffness occurred with RLC phosphorylation at 2.2-µm SL, but not at 1.9-µm SL, thereby suggesting that RLC phosphorylation increases β-myosin heavy chain binding or stiffness at longer SLs. The cross-bridge detachment rate slowed as SL increased, providing a potential mechanism for prolonged cross-bridge attachment to augment length-dependent activation of contraction at longer SLs. Length-dependent slowing of β-myosin heavy chain detachment rate was not affected by RLC phosphorylation. Together with our previous studies, these data suggest that both α- and β-myosin heavy chain isoforms show a length-dependent activation response and prolonged myosin attachment as SL increases in rat myocardial strips, and that RLC phosphorylation augments length-dependent activation at longer SLs. In comparing cardiac isoforms, however, we found that β-myosin heavy chain consistently showed greater length-dependent sensitivity than α-myosin heavy chain. Our work suggests that RLC phosphorylation is a vital contributor to the regulation of myocardial contractility in both cardiac myosin heavy chain isoforms.

scholarly journals Chronic hypoxia and VEGF differentially modulate abundance and organization of myosin heavy chain isoforms in fetal and adult ovine arteries

2012 ◽  
Vol 303 (10) ◽  
pp. C1090-C1103 ◽  
Author(s):  
Margaret C. Hubbell ◽  
Andrew J. Semotiuk ◽  
Richard B. Thorpe ◽  
Olayemi O. Adeoye ◽  
Stacy M. Butler ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Chronic Hypoxia ◽  
Myosin Heavy Chain Isoforms ◽  
Wall Structure ◽  
Vegf Receptor ◽  
Age Dependent ◽  
Endothelial Growth Factor

Chronic hypoxia increases vascular endothelial growth factor (VEGF) and thereby promotes angiogenesis. The present study explores the hypothesis that hypoxic increases in VEGF also remodel artery wall structure and contractility through phenotypic transformation of smooth muscle. Pregnant and nonpregnant ewes were maintained at sea level (normoxia) or 3,820 m (hypoxia) for the final 110 days of gestation. Common carotid arteries harvested from term fetal lambs and nonpregnant adults were denuded of endothelium and studied in vitro. Stretch-dependent contractile stresses were 32 and 77% of normoxic values in hypoxic fetal and adult arteries. Hypoxic hypocontractility was coupled with increased abundance of nonmuscle myosin heavy chain (NM-MHC) in fetal (+37%) and adult (+119%) arteries. Conversely, hypoxia decreased smooth muscle MHC (SM-MHC) abundance by 40% in fetal arteries but increased it 123% in adult arteries. Hypoxia decreased colocalization of NM-MHC with smooth muscle α-actin (SM-αA) in fetal arteries and decreased colocalization of SM-MHC with SM-αA in adult arteries. Organ culture with physiological concentrations (3 ng/ml) of VEGF-A165 similarly depressed stretch-dependent stresses to 37 and 49% of control fetal and adult values. The VEGF receptor antagonist vatalanib ablated VEGF's effects in adult but not fetal arteries, suggesting age-dependent VEGF receptor signaling. VEGF replicated hypoxic decreases in colocalization of NM-MHC with SM-αA in fetal arteries and decreases in colocalization of SM-MHC with SM-αA in adult arteries. These results suggest that hypoxic increases in VEGF not only promote angiogenesis but may also help mediate hypoxic arterial remodeling through age-dependent changes in smooth muscle phenotype and contractility.

scholarly journals Prdm1 (Blimp-1) and the Expression of Fast and Slow Myosin Heavy Chain Isoforms during Avian Myogenesis In Vitro

PLoS ONE ◽  
2010 ◽  
Vol 5 (4) ◽  
pp. e9951 ◽  
Author(s):  
Mary Lou Beermann ◽  
Magdalena Ardelt ◽  
Mahasweta Girgenrath ◽  
Jeffrey Boone Miller
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Myosin Heavy Chain Isoforms ◽  
Slow Myosin ◽  
Slow Myosin Heavy Chain

Myogenin, MyoD, and myosin expression after pharmacologically and surgically induced hypertrophy

1998 ◽  
Vol 84 (4) ◽  
pp. 1359-1364 ◽  
Author(s):  
P. E. Mozdziak ◽  
M. L. Greaser ◽  
E. Schultz
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Polyacrylamide Gel Electrophoresis ◽  
Myosin Heavy Chain Isoforms ◽  
Female Rats ◽  
Northern Analysis ◽  
Muscle Weight ◽  
Myosin Heavy Chain Isoform ◽  
Surgically Induced ◽  
Myod Expression

The relationship between myogenin or MyoD expression and hypertrophy of the rat soleus produced either by clenbuterol and 3,3′,5-triiodo-l-thyronine (CT) treatment or by surgical overload was examined. Mature female rats were subjected to surgical overload of the right soleus with the left soleus serving as a control. Another group received the same surgical treatment but were administered CT. Soleus muscles were harvested 4 wk after surgical overload and weighed. Myosin heavy chain isoforms were separated by using polyacrylamide gel electrophoresis while myogenin and MyoD expression were evaluated by Northern analysis. CT and functional overload increased soleus muscle weight. CT treatment induced the appearance of the fast type IIX myosin heavy chain isoform, depressed myogenin expression, and induced MyoD expression. However, functional overload did not alter myogenin or MyoD expression in CT-treated or non-CT-treated rats. Thus pharmacologically and surgically induced hypertrophy have differing effects on myogenin and MyoD expression, because their levels were associated with changes in myosin heavy chain composition (especially type IIX) rather than changes in muscle mass.

Role of microtubules versus myosin heavy chain isoforms in contractile dysfunction of hypertrophied murine cardiocytes

2003 ◽  
Vol 285 (3) ◽  
pp. H1270-H1285 ◽  
Author(s):  
Yuji Ishibashi ◽  
Masaru Takahashi ◽  
Yukihisa Isomatsu ◽  
Fei Qiao ◽  
Yoshihiro Iijima ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Contractile Function ◽  
Pressure Overload ◽  
Myosin Heavy Chain Isoforms ◽  
Left Ventricular ◽  
Contractile Dysfunction ◽  
Microtubule Depolymerization ◽  
Microtubule Network ◽  
Isoform Switching

In large mammals there is a correlation between microtubule network densification and contractile dysfunction in severe pressure-overload hypertrophy. In small mammals there is a similar correlation for the shift to β-myosin heavy chain (MHC), a MHC isoform having a slower ATPase Vmax. In this study, murine left ventricular (LV) pressure overload invoked both mechanisms: microtubule network densification and β-MHC expression. Cardiac β-MHC was also augmented without altering tubulin levels by two load-independent means, chemical thyroidectomy and transgenesis. In hypertrophy, contractile function of the LV and its cardiocytes decreased proportionally; microtubule depolymerization restored normal cellular contraction. In hypothyroid mice having a complete shift from α-MHC to β-MHC, contractile function of the LV and its cardiocytes also decreased, but microtubule depolymerization had no effect on cellular contraction. In transgenic mice having a cardiac β-MHC increase similar to that in hypertrophy, contractile function of the LV and its cardiocytes was normal, and microtubule depolymerization had no effect. Thus, although both mechanisms may cause contractile dysfunction, for the extent of MHC isoform switching seen even in severe murine LV pressure-overload hypertrophy, microtubule network densification appears to have the more important role.

scholarly journals Invited Review: Adaptive responses of skeletal muscle to intermittent hypoxia: the known and the unknown

2001 ◽  
Vol 90 (6) ◽  
pp. 2476-2487 ◽  
Author(s):  
Thomas L. Clanton ◽  
Paul F. Klawitter
Keyword(s):  
Skeletal Muscle ◽  
Intermittent Hypoxia ◽  
Contractile Function ◽  
Metabolic Enzyme ◽  
Cell Integrity ◽  
Adaptive Responses ◽  
Marine Animals ◽  
Obstructive Sleep ◽  
Low Levels

Intermittent hypoxia (IH) describes conditions of repeated, transient reductions in O2 that may trigger unique adaptations. Rest periods during IH may avoid potentially detrimental effects of long-term O2 deprivation. For skeletal muscle, IH can occur in conditions of obstructive sleep apnea, transient altitude exposures (with or without exercise), intermittent claudication, cardiopulmonary resuscitation, neonatal blood flow obstruction, and diving responses of marine animals. Although it is likely that adaptations in these conditions vary, some patterns emerge. Low levels of hypoxia shift metabolic enzyme activity toward greater aerobic poise; extreme hypoxia shifts metabolism toward greater anaerobic potential. Some conditions of IH may also inhibit lactate release during exercise. Many related cellular phenomena could be involved in the response, including activation of specific O2 sensors, reactive oxygen and nitrogen species, preconditioning, hypoxia-induced transcription factors, regulation of ion channels, and influences of paracrine/hormonal stimuli. The net effect of a variety of adaptive programs to IH may be to preserve contractile function and cell integrity in hypoxia or anoxia, a response that does not always translate into improvements in exercise performance.

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