Denervation enhances the physiological effects of the K<sub>ATP</sub> channel during fatigue in EDL and soleus muscle

Matar, Wadih Y.; Lunde, John A.; Jasmin, Bernard J.; Renaud, Jean‐Marc

doi:10.1152/ajpregu.2001.281.1.r56

Cited by 14 publications

(17 citation statements)

References 42 publications

(64 reference statements)

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“…The resulting decreases in membrane excitability and action potential amplitude lead to a decrease in Ca 2+ release and force (Burton and Smith, 1997;Duty and Allen, 1995;Gong et al, 2003;Matar et al, 2001;Weselcouch et al, 1993;Wickenden et al, 1996). The physiological benefit of a reduced Ca 2+ release would be reduced activity of Ca 2+ ATPases and myosin ATPases, thereby preserving ATP (Fig.…”

Section: Regulation and Impact Of The K Atp Channelmentioning

confidence: 99%

Skeletal muscle fatigue – regulation of excitation–contraction coupling to avoid metabolic catastrophe

MacIntosh¹,

Holash²,

Renaud³

2012

Journal of Cell Science

101

119

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Summary ATP provides the energy in our muscles to generate force, through its use by myosin ATPases, and helps to terminate contraction by pumping Ca 2+ back into the sarcoplasmic reticulum, achieved by Ca 2+ ATPase. The capacity to use ATP through these mechanisms is sufficiently high enough so that muscles could quickly deplete ATP. However, this potentially catastrophic depletion is avoided. It has been proposed that ATP is preserved not only by the control of metabolic pathways providing ATP but also by the regulation of the processes that use ATP. Considering that contraction (i.e. myosin ATPase activity) is triggered by release of Ca 2+ , the use of ATP can be attenuated by decreasing Ca 2+ release within each cell. A lower level of Ca 2+ release can be accomplished by control of membrane potential and by direct regulation of the ryanodine receptor (RyR, the Ca 2+ release channel in the terminal cisternae). These highly redundant control mechanisms provide an effective means by which ATP can be preserved at the cellular level, avoiding metabolic catastrophe. This Commentary will review some of the known mechanisms by which this regulation of Ca 2+ release and contractile response is achieved, demonstrating that skeletal muscle fatigue is a consequence of attenuation of contractile activation; a process that allows avoidance of metabolic catastrophe.Key words: Endurance, Membrane excitability, Skeletal muscle contraction Introduction Typically, when exercise scientists think of control of skeletal muscle contraction, they consider motor unit recruitment and rate coding, the primary means by which the brain regulates the magnitude of muscle contraction. However, the magnitude of skeletal muscle contraction can also be regulated at the cellular level. This level of control is necessary to avoid cellular metabolic catastrophe, i.e. the situation in which ATP depletion reaches a level that is damaging to the fiber.ATP is the common final source for energy in the cell, and its concentration [along with the concentrations of ADP and inorganic phosphate (Pi)] affects the magnitude of energy that is made available from its hydrolysis. At rest, skeletal muscle has a low metabolic rate, not unlike many other passive tissues, and the intracellular concentration of ATP is in the 5-7 mM range (Hochachka and Matheson, 1992). However, during muscle activity, there are three major ATPases that require ATP for their function (Box 1); during exercise, skeletal muscle can increase its rate of ATP use by more than 100 times (Hochachka and McClelland, 1997), a rate that is much faster than can be replenished by aerobic metabolism. This latter point is clear from the fact that the muscle power output can greatly exceed the level that can be supported by aerobic metabolism (MacIntosh et al., 2000). To accommodate this additional energy requirement, ATP is provided by non-aerobic means (through phosphocreatine hydrolysis and glycolysis resulting in lactate formation), but this alternative source of ATP has limited capacity (Monod ...

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Section: Regulation and Impact Of The K Atp Channelmentioning

confidence: 99%

Skeletal muscle fatigue – regulation of excitation–contraction coupling to avoid metabolic catastrophe

MacIntosh¹,

Holash²,

Renaud³

2012

Journal of Cell Science

101

119

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“…Many of the articles cited here present repeated-measurements data that are quite nonlinear (e.g., Refs. 7,16,17,19,20,26,30,31,35), so it seems natural to try to model the data by using nonlinear models. Above, it was argued that, if the force decay was exponential, log-transforming the response would yield a linear model.…”

Section: Nonlinear Modelsmentioning

confidence: 99%

“…3,[7][8][9]12,13,[15][16][17]19,20,[23][24][25][26][30][31][32]35,37). Descriptions of the experimental protocols and various figures showing the data suggest that many studies in the archives of, for example, the journals published by the American Physiological Society and the references cited above are published wherein somewhat inappropriate statistical properties of the data are assumed (but see, e.g., Refs.…”

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confidence: 99%

Statistical analyses of repeated measures in physiological research: a tutorial

Kristensen

Hansen

2004

Advances in Physiology Education

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Experimental designs involving repeated measurements on experimental units are widely used in physiological research. Often, relatively many consecutive observations on each experimental unit are involved and the data may be quite nonlinear. Yet evidently, one of the most commonly used statistical methods for dealing with such data sets in physiological research is the repeated-measurements ANOVA model. The problem herewith is that it is not well suited for data sets with many consecutive measurements; it does not deal with nonlinear features of the data, and the interpretability of the model may be low. The use of inappropriate statistical models increases the likelihood of drawing wrong conclusions. The aim of this article is to illustrate, for a reasonably typical repeated-measurements data set, how fundamental assumptions of the repeated-measurements ANOVA model are inappropriate and how researchers may benefit from adopting different modeling approaches using a variety of different kinds of models. We emphasize intuitive ideas rather than mathematical rigor. We illustrate how such models represent alternatives that 1) can have much higher interpretability, 2) are more likely to meet underlying assumptions, 3) provide better fitted models, and 4) are readily implemented in widely distributed software products.

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“…Since the efficacy of KATP channel opener and the relative contribution of KATP channel to total K + conductance increase in denervated muscle [14,23], activation of KATP channels would inhibit fibrillating potentials and curtail Ca 2+ release from the SR, accounting for the relaxation of basal tone and depression of twitch force. By contrast, contractures resulted from direct mobilization of SR Ca 2+ were not affected, suggesting that the contractile machineries and SR Ca 2+ content are not significantly altered within 2 weeks of denervation.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Cyclopiazonic Acid-Mediated Contracture of Mouse Diaphragm after Denervation

Hong¹,

Liang²,

Shen³

2005

Pharmacology

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As a major Ca²⁺ source for muscle contraction, the sarcoplasmic reticulum (SR) of skeletal muscle maintains its Ca²⁺ content by uptake of myoplasmic Ca²⁺ and by replenishment with extracellular Ca²⁺. Since transection of motor nerve alters the functions of SR Ca²⁺ pump and sarcolemma ion channels, this study explored the effect of denervation on the contracture evoked by cyclopiazonic acid (CPA), an inhibitor of SR Ca²⁺ pump. In innervated hemidiaphragm, CPA elicited a bimodal elevation of muscle tone, which was dependent on extracellular Ca²⁺ and differentially inhibited by pretreatment with 2-aminoethoxydiphenylborane (APB) and U73122. Activation of muscle Na⁺ channels to simulate denervation-induced membrane depolarization did not change the contracture profile. After denervation for 5–14 days when the contracture induced by caffeine was not yet depressed, CPA elicited only APB-sensitive monophasic contracture. Stimulation of ATP-regulated K⁺ channels with lemakalim hyperpolarized muscle membrane and attenuated CPA contracture in denervated, but not innervated, hemidiaphragm. The effects of lemakalim were antagonized by glybenclamide. It is inferred that the bimodal CPA contracture is resulted from distinct recruitments of Ca²⁺ entry and that denervation alters the voltage dependence and down-regulates CPA-mediated Ca²⁺ influx.

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Denervation enhances the physiological effects of the K_ATP channel during fatigue in EDL and soleus muscle

Cited by 14 publications

References 42 publications

Skeletal muscle fatigue – regulation of excitation–contraction coupling to avoid metabolic catastrophe

Skeletal muscle fatigue – regulation of excitation–contraction coupling to avoid metabolic catastrophe

Statistical analyses of repeated measures in physiological research: a tutorial

Alteration of Cyclopiazonic Acid-Mediated Contracture of Mouse Diaphragm after Denervation

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Denervation enhances the physiological effects of the KATP channel during fatigue in EDL and soleus muscle

Cited by 14 publications

References 42 publications

Skeletal muscle fatigue – regulation of excitation–contraction coupling to avoid metabolic catastrophe

Skeletal muscle fatigue – regulation of excitation–contraction coupling to avoid metabolic catastrophe

Statistical analyses of repeated measures in physiological research: a tutorial

Alteration of Cyclopiazonic Acid-Mediated Contracture of Mouse Diaphragm after Denervation

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Denervation enhances the physiological effects of the K_ATP channel during fatigue in EDL and soleus muscle