Effects of Acidosis on Maximum Shortening Velocity and Force-Velocity Relation of Skinned Rat Cardiac Muscle

Ricciardi, L; Bottinelli, Roberto; Canepari, Monica; Reggiani, Carlo

doi:10.1006/jmcc.1994.1072

Cited by 12 publications

(14 citation statements)

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“…With the duration of these putative nonproductive binding events at pH 6.4 being sensitive to ATP, the effective load presented by these events would be greater at lower ATP concentrations. This internal load might explain the rightward shift in the V actin /[ATP] relationship and therefore the apparent change in K m , supporting the hypothesis that acidosis slows V max in muscle fibers by imposing an increased resistive drag (36).…”

Section: Low Ph Increases Nonproductive Actomyosin Interactionsmentioning

confidence: 87%

Effect of low pH on single skeletal muscle myosin mechanics and kinetics

Debold¹,

Beck²,

Warshaw³

2008

American Journal of Physiology-Cell Physiology

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Acidosis (low pH) is the oldest putative agent of muscular fatigue, but the molecular mechanism underlying its depressive effect on muscular performance remains unresolved. Therefore, the effect of low pH on the molecular mechanics and kinetics of chicken skeletal muscle myosin was studied using in vitro motility (IVM) and single molecule laser trap assays. Decreasing pH from 7.4 to 6.4 at saturating ATP slowed actin filament velocity (V(actin)) in the IVM by 36%. Single molecule experiments, at 1 microM ATP, decreased the average unitary step size of myosin (d) from 10 +/- 2 nm (pH 7.4) to 2 +/- 1 nm (pH 6.4). Individual binding events at low pH were consistent with the presence of a population of both productive (average d = 10 nm) and nonproductive (average d = 0 nm) actomyosin interactions. Raising the ATP concentration from 1 microM to 1 mM at pH 6.4 restored d (9 +/- 3 nm), suggesting that the lifetime of the nonproductive interactions is solely dependent on the [ATP]. V(actin), however, was not restored by raising the [ATP] (1-10 mM) in the IVM assay, suggesting that low pH also prolongs actin strong binding (t(on)). Measurement of t(on) as a function of the [ATP] in the single molecule assay suggested that acidosis prolongs t(on) by slowing the rate of ADP release. Thus, in a detachment limited model of motility (i.e., V(actin) approximately d/t(on)), a slowed rate of ADP release and the presence of nonproductive actomyosin interactions could account for the acidosis-induced decrease in V(actin), suggesting a molecular explanation for this component of muscular fatigue.

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Section: Low Ph Increases Nonproductive Actomyosin Interactionsmentioning

confidence: 87%

Effect of low pH on single skeletal muscle myosin mechanics and kinetics

Debold¹,

Beck²,

Warshaw³

2008

American Journal of Physiology-Cell Physiology

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“…Acidosis decreases both maximal Ca 2ϩ -activated tension and the Ca 2ϩ sensitivity of tension (2,20,23,31,32,47). Acidosis also decreases myocyte maximal sarcomere length shortening amplitude and shortening velocity (20,48,49). These experiments illustrate that myofilament Ca 2ϩ desensitization at low pH is a fundamental molecular deficiency responsible for cardiac organ pathologies associated with myocardial acidosis (9).…”

Section: Myofilament Calcium Sensitivity and Acidosismentioning

confidence: 91%

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo

2009

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Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO(2) challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a beta-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any beta-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.

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“…Increases in H ϩ (i.e., acidosis) that occur during ischemia also decrease cardiac myocyte function. In contrast to P i , H ϩ has been reported to decrease unloaded and loaded shortening velocity in cardiac trabeculae preparations (33) in addition to decreasing isometric force production (10,17,24,30). Studies examining increases of both P i and H ϩ working in concert have primarily been limited to assessments of alterations in force production (17,29,39).…”

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confidence: 99%

β-Myosin heavy chain myocytes are more resistant to changes in power output induced by ischemic conditions

Hinken

McDonald

2006

American Journal of Physiology-Heart and Circulatory Physiology

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During ischemia intracellular concentrations of P(i) and H+ increase. Also, changes in myosin heavy chain (MHC) isoform toward beta-MHC have been reported after ischemia and infarction associated with coronary artery disease. The purpose of this study was to investigate the effects of myoplasmic changes of P(i) and H+ on the loaded shortening velocity and power output of cardiac myocytes expressing either alpha- or beta-MHC. Skinned cardiac myocyte preparations were obtained from adult male Sprague-Dawley rats (control or treated with 5-n-propyl-2-thiouracil to induce beta-MHC) and mounted between a force transducer and servomotor system. Myocyte preparations were subjected to a series of isotonic force clamps to determine shortening velocity and power output during Ca2+ activations in each of the following solutions: 1) pCa 4.5 and pH 7.0; 2) pCa 4.5, pH 7.0, and 5 mM P(i); 3) pCa 4.5 and pH 6.6; and 4) pCa 4.5, pH 6.6, and 5 mM P(i). Added P(i) and lowered pH each caused isometric force to decline to the same extent in alpha-MHC and beta-MHC myocytes; however, beta-MHC myocytes were more resistant to changes in absolute power output. For example, peak absolute power output fell 53% in alpha-MHC myocytes, whereas power fell only 38% in beta-MHC myocytes in response to elevated P(i) and lowered pH (i.e., solution 4). The reduced effect on power output was the result of a greater increase in loaded shortening velocity induced by P(i) in beta-MHC myocytes and an increase in loaded shortening velocity at pH 6.6 that occurred only in beta-MHC myocytes. We conclude that the functional response to elevated P(i) and lowered pH during ischemia is MHC isoform-dependent with beta-MHC myocytes being more resistant to declines in power output.

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Effects of Acidosis on Maximum Shortening Velocity and Force-Velocity Relation of Skinned Rat Cardiac Muscle

Cited by 12 publications

References 0 publications

Effect of low pH on single skeletal muscle myosin mechanics and kinetics

Effect of low pH on single skeletal muscle myosin mechanics and kinetics

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo

β-Myosin heavy chain myocytes are more resistant to changes in power output induced by ischemic conditions

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