Wheel-running exercise alters rat diaphragm action potentials and their regulation by K+ channels

2003 ◽  
Vol 95 (2) ◽  
pp. 602-610 ◽  
Author(s):  
Erik van Lunteren ◽  
Michelle Moyer
Keyword(s):  
Skeletal Muscle ◽  
Ion Channels ◽  
Action Potential ◽  
Endurance Exercise ◽  
Wheel Running ◽  
Diaphragm Muscle ◽  
Resting Membrane Potential ◽  
Free Access ◽  
Diaphragm Action ◽  
Action Potential Repolarization

Endurance exercise modifies regulatory systems that control skeletal muscle Na+ and K+ fluxes, in particular Na+-K+-ATPase-mediated transport of these ions. Na+ and K+ ion channels also play important roles in the regulation of ionic movements, specifically mediating Na+ influx and K+ efflux that occur during contractions resulting from action potential depolarization and repolarization. Whether exercise alters skeletal muscle electrophysiological properties controlled by these ion channels is unclear. The present study tested the hypothesis that endurance exercise modifies diaphragm action potential properties. Exercised rats spent 8 wk with free access to running wheels, and they were compared with sedentary rats living in conventional rodent housing. Diaphragm muscle was subsequently removed under anesthesia and studied in vitro. Resting membrane potential was not affected by endurance exercise. Muscle from exercised rats had a slower rate of action potential repolarization than that of sedentary animals ( P = 0.0098), whereas rate of depolarization was similar in the two groups. The K+ channel blocker 3,4-diaminopyridine slowed action potential repolarization and increased action potential area of both exercised and sedentary muscle. However, these effects were significantly smaller in diaphragm from exercised than sedentary rats. These data indicate that voluntary running slows diaphragm action potential repolarization, most likely by modulating K+ channel number or function.

scholarly journals Understanding the physiology of the asymptomatic diaphragm of the M1592V hyperkalemic periodic paralysis mouse

2015 ◽  
Vol 146 (6) ◽  
pp. 509-525 ◽  
Author(s):  
Tarek Ammar ◽  
Wei Lin ◽  
Amanda Higgins ◽  
Lawrence J. Hayward ◽  
Jean-Marc Renaud
Keyword(s):  
Action Potential ◽  
Periodic Paralysis ◽  
Diaphragm Muscle ◽  
Resting Membrane Potential ◽  
Action Potential Amplitude ◽  
Wild Type ◽  
Hyperkalemic Periodic Paralysis ◽  
Potential Amplitude ◽  
Reverse Mode ◽  
Diaphragm Action

The diaphragm muscle of hyperkalemic periodic paralysis (HyperKPP) patients and of the M1592V HyperKPP mouse model rarely suffers from the myotonic and paralytic symptoms that occur in limb muscles. Enigmatically, HyperKPP diaphragm expresses the mutant NaV1.4 channel and, more importantly, has an abnormally high Na+ influx similar to that in extensor digitorum longus (EDL) and soleus, two hindlimb muscles suffering from the robust HyperKPP abnormalities. The objective was to uncover the physiological mechanisms that render HyperKPP diaphragm asymptomatic. A first mechanism involves efficient maintenance of resting membrane polarization in HyperKPP diaphragm at various extracellular K+ concentrations compared with larger membrane depolarizations in HyperKPP EDL and soleus. The improved resting membrane potential (EM) results from significantly increased Na+ K+ pump electrogenic activity, and not from an increased protein content. Action potential amplitude was greater in HyperKPP diaphragm than in HyperKPP soleus and EDL, providing a second mechanism for the asymptomatic behavior of the HyperKPP diaphragm. One suggested mechanism for the greater action potential amplitude is lower intracellular Na+ concentration because of greater Na+ K+ pump activity, allowing better Na+ current during the action potential depolarization phase. Finally, HyperKPP diaphragm had a greater capacity to generate force at depolarized EM compared with wild-type diaphragm. Action potential amplitude was not different between wild-type and HyperKPP diaphragm. There was also no evidence for an increased activity of the Na+–Ca2+ exchanger working in the reverse mode in the HyperKPP diaphragm compared with the wild-type diaphragm. So, a third mechanism remains to be elucidated to fully understand how HyperKPP diaphragm generates more force compared with wild type. Although the mechanism for the greater force at depolarized resting EM remains to be determined, this study provides support for the modulation of the Na+ K+ pump as a component of therapy to alleviate weakness in HyperKPP.

scholarly journals Srf KO and wild-type mice similarly adapt to endurance exercise

2019 ◽  
Vol 29 (2) ◽  
Author(s):  
Haidar Djemai ◽  
Medhi Hassani ◽  
Nissrine Daou ◽  
Zhenlin Li ◽  
Athanassia Sotiropoulos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Serum Response Factor ◽  
Wheel Running ◽  
Voluntary Exercise ◽  
Muscle Performance ◽  
Adaptive Responses ◽  
Aerobic Activity ◽  
Exercise Adaptation ◽  
Muscle Homeostasis

Physical exercise has important effects as secondary prevention or intervention against several diseases. Endurance exercise induces local and global effects, resulting in skeletal muscle adaptations to aerobic activity and contributes to an amelioration of muscle performance. Furthermore, it prevents muscle loss. Serum response factor (Srf) is a transcription factor of pivotal importance for muscle tissues and animal models of Srf genetic deletion/over-expression are widely used to study Srf role in muscle homeostasis, physiology and pathology. A global characterisation of exercise adaptation in the absence of Srf has not been reported. We measured body composition, muscle force, running speed, energy expenditure and metabolism in WT and inducible skeletal muscle-specific Srf KO mice, following three weeks of voluntary exercise by wheel running. We found a major improvement in the aerobic capacity and muscle function in WT mice following exercise, as expected, and no major differences were observed in Srf KO mice as compared to WT mice, following exercise. Taken together, these observations suggest that Srf is not required for an early (within 3 weeks) adaptation to spontaneous exercise and that Srf KO mice behave similarly to the WT in terms of spontaneous physical activity and the resulting adaptive responses. Therefore, Srf KO mice can be used in functional muscle studies, without the results being affected by the lack of Srf. Since lack of Srf induces premature sarcopenia, our observations suggest that the modifications due to the absence of Srf take time to occur and that young, Srf KO mice behave similarly to WT in aerobic physical activities.

scholarly journals Calcineurin activates interleukin-6 transcription in mouse skeletal muscle in vivo and in C2C12 myotubes in vitro

2010 ◽  
Vol 298 (1) ◽  
pp. R198-R210 ◽  
Author(s):  
David L. Allen ◽  
Jill J. Uyenishi ◽  
Allison S. Cleary ◽  
Ryan S. Mehan ◽  
Sarah F. Lindsay ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Binding Sites ◽  
Promoter Activity ◽  
Wheel Running ◽  
Mrna Levels ◽  
Dna Binding Sites ◽  
Single Bout

Expression of the cytokine interleukin-6 (IL-6) by skeletal muscle is hugely increased in response to a single bout of endurance exercise, and this appears to be mediated by increases in intracellular calcium. We examined the effects of endurance exercise on IL-6 mRNA levels and promoter activity in skeletal muscle in vivo, and the role of the calcium-activated calcineurin signaling pathway on muscle IL-6 expression in vivo and in vitro. IL-6 mRNA levels in the mouse tibialis anterior (TA) were increased 2–10-fold by a single bout of treadmill exercise or by 3 days of voluntary wheel running. Moreover, an IL-6 promoter-driven luciferase transgene was activated in TA by both treadmill and wheel-running exercise and by injection with a calcineurin plasmid. Exercise also increased muscle mRNA expression of the calcineurin regulatory gene MCIP1, as did treatment of C2C12 myotubes with the calcium ionophore A23187. Cotransfection of C2C12 myotubes with a constitutively active calcineurin construct significantly increased while cotransfection with the calcineurin inhibitor CAIN inhibited activity of a mouse IL-6 promoter-reporter construct. Cotransfection with a myocyte enhancer-factor-2 (MEF-2) expression construct increased basal IL-6 promoter activity and augmented the effects of calcineurin cotransfection, while cotransfection with the MEF-2 antagonist MITR repressed calcineurin-activated IL-6 promoter activity in vitro. Surprisingly, cotransfection with a dominant-negative form of another calcineurin-activated transcription factor, nuclear factor activator of T cells (NFAT), greatly potentiated both basal and calcineurin-stimulated IL-6 promoter activity in C2C12 myotubes. Mutation of the MEF-2 DNA binding sites attenuated, while mutation of the NFAT DNA binding sites potentiated basal and calcineurin-activated IL-6 promoter activity. Finally, CREB and C/EBP were necessary for basal IL-6 promoter activity and sufficient to increase IL-6 promoter activity but had minimal roles in calcineurin-activated IL-6 promoter activity. Together, these results suggest that IL-6 transcription in skeletal muscle cells can be activated by a calcineurin-MEF-2 axis which is antagonized by NFAT.

scholarly journals An inducible knockout of Dicer in adult mice does not affect endurance exercise-induced muscle adaptation

2019 ◽  
Vol 316 (2) ◽  
pp. C285-C292 ◽  
Author(s):  
Satoshi Oikawa ◽  
Minjung Lee ◽  
Norio Motohashi ◽  
Seiji Maeda ◽  
Takayuki Akimoto
Keyword(s):  
Skeletal Muscle ◽  
Endurance Exercise ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Fiber Type ◽  
Tamoxifen Treatment ◽  
Muscle Adaptation ◽  
Adult Skeletal Muscle ◽  
Significant Difference ◽  
Exercise Induced

The contractile and metabolic properties of adult skeletal muscle change in response to endurance exercise. The mechanisms of transcriptional regulation in exercise-induced skeletal muscle adaptation, including fiber-type switching and mitochondrial biogenesis, have been investigated intensively, whereas the role of microRNA (miRNA)-mediated posttranscriptional gene regulation is less well understood. We used tamoxifen-inducible Dicer1 knockout (iDicer KO) mice to reduce the global expression of miRNAs in adult skeletal muscle and subjected these mice to 2 wk of voluntary wheel running. Dicer mRNA expression was completely depleted in fast-twitch plantaris muscle after tamoxifen injection. However, several muscle-enriched miRNAs, including miR-1 and miR-133a, were reduced by only 30–50% in both the slow and fast muscles. The endurance exercise-induced changes that occurred for many parameters (i.e., fast-to-slow fiber-type switch and increases in succinate dehydrogenase, respiratory chain complex II, and citrate synthase activity) in wild type (WT) also occurred in the iDicer KO mice. Protein expression of myosin heavy chain IIa, peroxisome proliferator-activated receptor-γ coactivator-1α, and cytochrome c complex IV was also increased in the iDicer KO mice by the voluntary running. Furthermore, there was no significant difference in oxygen consumption rate in the isolated mitochondria between the WT and iDicer KO mice. These data indicate that muscle-enriched miRNAs were detectable even after 4 wk of tamoxifen treatment and there was no apparent specific endurance-exercise-induced muscle phenotype in the iDicer KO mice.

scholarly journals Effect of obesity and exercise on the expression of the novel myokines, Myonectin and Irisin

2014 ◽  
Author(s):  
Jonathan M Peterson ◽  
Ryan Mart ◽  
Cherie E Bond
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Reference Genes ◽  
Effective Means ◽  
Expression Level ◽  
Diaphragm Muscle ◽  
Pcr Analysis ◽  
Zucker Rat

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, Myonectin and Fibronectin type III domain containing 5 (Fndc5), the precursor for Irisin. Methods: We used the diaphragm muscle from both the obese Zucker rat (OZR) and lean Zucker Rat (LZR) with 9 weeks of aerobic training on a motorized treadmill. We examined the gene expression of 12 commonly used reference genes and performed quantitative real-time PCR analysis on the gene expression of Myonectin and Fndc5. Results: Of the 12 commonly used PCR reference genes tested we were able to establish that Hypoxanthine phosphoribosyltransferase 1 (HPRT1) and lactate dehydrogenase A (Ldha) remained stable in the diaphragm muscle regardless of obesity or exercise training. Interestingly, we also concluded that the commonly used reference genes: beta-Actin, beta-2-microglobulin, Non-POU domain containing, octamer-binding, Peptidylprolyl isomerase H, 18S ribosomal rna, TATA box binding protein and Transferrin receptor were all found to be altered by the combination of exercise and obesity. Our study showed that the diaphragm muscle of the OZR had significantly higher expression levels of both myonectin and Fndc5. Exercise training had no effect on the expression level of Fndc5, but significantly lowered the gene expression of myonectin in both the LZR and OZR groups. Conclusion: Contrary to prior findings regarding the regulation of Fndc5 and myonectin we show that myonectin and Fndc5 expression are both increased in the OZR model of obesity. Further, long-term exercise training decreases myonectin levels, which is opposite, the effect reported with short-term exercise. However, this report confirms earlier work showing that Fndc5 gene expression is not altered by chronic exercise.

scholarly journals Effect of obesity and exercise on the expression of the novel myokines, Myonectin and Irisin

2014 ◽  
Author(s):  
Jonathan M Peterson ◽  
Ryan Mart ◽  
Cherie E Bond
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Reference Genes ◽  
Effective Means ◽  
Expression Level ◽  
Diaphragm Muscle ◽  
Pcr Analysis ◽  
Zucker Rat

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, Myonectin and Fibronectin type III domain containing 5 (Fndc5), the precursor for Irisin. Methods: We used the diaphragm muscle from both the obese Zucker rat (OZR) and lean Zucker Rat (LZR) with 9 weeks of aerobic training on a motorized treadmill. We examined the gene expression of 12 commonly used reference genes and performed quantitative real-time PCR analysis on the gene expression of Myonectin and Fndc5. Results: Of the 12 commonly used PCR reference genes tested we were able to establish that Hypoxanthine phosphoribosyltransferase 1 (HPRT1) and lactate dehydrogenase A (Ldha) remained stable in the diaphragm muscle regardless of obesity or exercise training. Interestingly, we also concluded that the commonly used reference genes: beta-Actin, beta-2-microglobulin, Non-POU domain containing, octamer-binding, Peptidylprolyl isomerase H, 18S ribosomal rna, TATA box binding protein and Transferrin receptor were all found to be altered by the combination of exercise and obesity. Our study showed that the diaphragm muscle of the OZR had significantly higher expression levels of both myonectin and Fndc5. Exercise training had no effect on the expression level of Fndc5, but significantly lowered the gene expression of myonectin in both the LZR and OZR groups. Conclusion: Contrary to prior findings regarding the regulation of Fndc5 and myonectin we show that myonectin and Fndc5 expression are both increased in the OZR model of obesity. Further, long-term exercise training decreases myonectin levels, which is opposite, the effect reported with short-term exercise. However, this report confirms earlier work showing that Fndc5 gene expression is not altered by chronic exercise.

How to sample the entire length of a single muscle fiber quick-frozen after electrical point stimulation for high resolution EM

1992 ◽  
Vol 50 (1) ◽  
pp. 776-777
Author(s):  
Joachim R. Sommer ◽  
Teresa High ◽  
Betty Scherer ◽  
Isaiah Taylor ◽  
Rashid Nassar
Keyword(s):  
Skeletal Muscle ◽  
High Resolution ◽  
Action Potential ◽  
Muscle Fiber ◽  
Freeze Fracture ◽  
Freeze Substitution ◽  
Electrical Field Stimulation ◽  
Skeletal Muscle Fiber ◽  
Freeze Dried ◽  
Quick Freezing

We have developed a model that allows the quick-freezing at known time intervals following electrical field stimulation of a single, intact frog skeletal muscle fiber isolated by sharp dissection. The preparation is used for studying high resolution morphology by freeze-substitution and freeze-fracture and for electron probe x-ray microanlysis of sudden calcium displacement from intracellular stores in freeze-dried cryosections, all in the same fiber. We now show the feasibility and instrumentation of new methodology for stimulating a single, intact skeletal muscle fiber at a point resulting in the propagation of an action potential, followed by quick-freezing with sub-millisecond temporal resolution after electrical stimulation, followed by multiple sampling of the frozen muscle fiber for freeze-substitution, freeze-fracture (not shown) and cryosectionmg. This model, at once serving as its own control and obviating consideration of variances between different fibers, frogs etc., is useful to investigate structural and topochemical alterations occurring in the wake of an action potential.

Effect of low chloride on relaxation in hamster diaphragm muscle

1986 ◽  
Vol 61 (1) ◽  
pp. 180-184 ◽  
Author(s):  
S. A. Esau ◽  
N. Sperelakis
Keyword(s):  
Membrane Potential ◽  
Muscle Fatigue ◽  
Time Constant ◽  
Diaphragm Muscle ◽  
Resting Membrane Potential ◽  
Krebs Solution ◽  
Sarcolemmal Membrane ◽  
Cl Conductance

With muscle fatigue the chloride (Cl-) conductance of the sarcolemmal membrane decreases. The role of lowered Cl- conductance in the prolongation of relaxation seen with fatigue was studied in isolated hamster diaphragm strips. The muscles were studied in either a Krebs solution or a low Cl- solution in which half of the NaCl was replaced by Na-gluconate. Short tetanic contractions were produced by a 160-ms train of 0.2-ms pulses at 60 Hz from which tension (T) and the time constant of relaxation were measured. Resting membrane potential (Em) was measured using KCl-filled microelectrodes with resistances of 15–20 M omega. Mild fatigue (20% fall in tension) was induced by 24–25 tetanic contractions at the rate of 2/s. There was no difference in Em or T in the two solutions, either initially or with fatigue. The time constant of relaxation was greater in low Cl- solution, both initially (22 +/- 3 vs. 18 +/- 5 ms, mean +/- SD, P less than 0.05) and with fatigue (51 +/- 18 vs. 26 +/- 7 ms, P less than 0.005). Lowering of sarcolemmal membrane Cl- conductance appears to play a role in the slowing of relaxation of hamster diaphragm muscle seen with fatigue.

scholarly journals Paternal High Fat Diet and Exercise Differentially Regulate Placental Development and Inflammation in a Sex-Specific Manner in C57BL6/J Mice (P19-003-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kate Larson ◽  
Amy Bundy ◽  
Travis Alvine ◽  
James Roemmich
Keyword(s):  
Skeletal Muscle ◽  
Agricultural Research ◽  
Wheel Running ◽  
Fetal Weight ◽  
High Fat ◽  
Placental Development ◽  
Funding Sources ◽  
Service Project ◽  
Diet And Exercise ◽  
Placental Inflammation

Abstract Objectives We have shown that increases in T2D risk in male offspring when the father consumes a high-fat (HF) diet can be normalized when the father also exercises during preconception, and that this protection may occur by epigenetic increases in insulin signaling within offspring skeletal muscle. In our current study, we investigated to determine how paternal HF diet and exercise conditions alter sperm miRNA, fetal weight and placental inflammation. Methods Three-week old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or a HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF diet fed dams. Sperm samples were collected to determine changes in miRNA that may account for the enhanced offspring skeletal muscle responses that helped normalize paternal HF-induced glucose intolerance. Placentae were collected to determine whether changes in sperm miRNA expression differed by amount of placental inflammation. Results Sperm expression of miRNA 193b increased with paternal HF and exercise. In F1 males, placental and fetal weight decreased with HF diet while, in F1 female, paternal HF and exercise had no effect on placental and fetal weights. Paternal HF diet decreased placental IL-6 and TNF-alpha mRNA expression in F1 females, while no effects were observed in F1 male placenta. Conclusions Taken together these data suggest that paternal HF diet has a greater impact on placental development of male fetuses while paternal exercise has greater impact on placental inflammation of female fetuses. For both female and male fetuses, these paternal influences are mediated via sperm miRNA 193b. miR-193b is involved in regulation of the cell cycle and adipogenesis but may have additional functions. Thus, the exact role of sperm miRNA 193b in sex-specific epigenetic transmission of paternal HF diet and exercise on placental and fetal development needs further evaluation. Funding Sources USDA Agricultural Research Service Project #3062-51000-052-00D.

Sign in / Sign up

Export Citation Format

Share Document