The depressive effect of P_i on the force-pCa relationship in skinned single muscle fibers is temperature dependent

Abstract

. The depressive effect of P i on the force-pCa relationship in skinned single muscle fibers is temperature dependent. Am J Physiol Cell Physiol 290: C1041-C1050, 2006. First published November 9, 2005 doi:10.1152/ajpcell.00342.2005.-Increases in P i combined with decreases in myoplasmic Ca 2ϩ are believed to cause a significant portion of the decrease in muscular force during fatigue. To investigate this further, we determined the effect of 30 mM Pi on the force-Ca 2ϩ relationship of chemically skinned single muscle fibers at near-physiological temperature (30°C). Fibers isolated from rat soleus (slow) and gastrocnemius (fast) muscle were subjected to a series of solutions with an increasing free Ca 2ϩ concentration in the presence and absence of 30 mM Pi at both low (15°C) and high (30°C) temperature. In slow fibers, 30 mM P i significantly increased the Ca 2ϩ required to elicit measurable force, referred to as the activation threshold at both low and high temperatures; however, the effect was twofold greater at the higher temperature. In fast fibers, the activation threshold was unaffected by elevating P i at 15°C but was significantly increased at 30°C. At both low and high temperatures, 30 mM P i increased the Ca 2ϩ required to elicit half-maximal force (pCa50) in both slow and fast fibers, with the effect of P i twofold greater at the higher temperature. These data suggest that during fatigue, reductions in the myoplasmic Ca 2ϩ and increases in Pi act synergistically to reduce muscular force. Consequently, the combined changes in these ions likely account for a greater portion of fatigue than previously predicted based on studies at lower temperatures or high temperatures at saturating Ca 2ϩ levels.force-pCa relationship; phosphate; fatigue HIGH-FREQUENCY STIMULATION of skeletal muscle results in a rapid loss of force and power, with the steepest decline occurring during the later stages of fatigue. This is attributed, at least in part, to elevated levels of P i resulting from the rapid breakdown of ATP and creatine phosphate. In addition, decreases in the intracellular levels of Ca 2ϩ as a result of compromised Ca 2ϩ release also act to reduce force and power (1,2,20). Changes in these ions also may act synergistically to produce even further reductions in force.During intense muscle contraction, a strong inverse correlation exists between muscular force and P i , an observation that supports the hypothesis that increases in intracellular P i at least in part induce fatigue (20,52). This hypothesis stemmed from experiments in single skinned fibers demonstrating that elevated P i reduces isometric force in nonexercised fibers at saturating Ca 2ϩ concentrations (7-9, 36, 38, 39, 42). At a typical fatiguing concentration of 30 mM P i , maximal isometric force (P o ) can be depressed by Ͼ50% compared with near-zero P i in single mammalian fibers (44).In addition to changes in P i , myoplasmic free Ca 2ϩ concentration declines during fatigue, resulting from a decrease in the amount of Ca 2ϩ released from the ...

Micromechanical Thermal Assays of Ca2+-Regulated Thin-Filament Function and Modulation by Hypertrophic Cardiomyopathy Mutants of Human Cardiac Troponin

“…Temperature has previously been shown to modulate the effect of Pi on isometric force in muscle fibers, although there is disagreement about whether Pi is either more [29, 76] or less [77] inhibitory of isometric force as temperature increases. While Pi inhibits isometric force, elevated Pi increases sliding speed for both regulated thin filaments at pCa 5 and unregulated F-actin, although the effect predominates at lower temperatures and is more pronounced for regulated thin-filaments (Figure 5).…”

“…It affects several fundamental aspects of muscle structure and function [22–24] although temperature effects on muscle function appear to be greater at low temperatures used in many experiments than at physiological temperature; examples are isometric tetanic tension [25–27] and maximum mechanical power output [28]. Temperature also modulates the control of striated muscle contraction by Ca 2+ regulatory proteins Tn and Tm, although there are both qualitative and quantitative discrepancies on this point in the striated muscle literature [22, 26, 29, 30]. Interestingly, mild hypothermia has been reported to be a positive inotropic effector in living cardiac muscle due to interplay between temperature and cardiac thin filament Ca 2+ regulation [31].…”

Low cell pH depresses peak power in rat skeletal muscle fibres at both 30°C and 15°C: implications for muscle fatigue

“…• C (Debold et al 2006). If pH were to show similar temperature dependence, the force-inhibiting effect of low pH at suboptimal Ca 2+ concentrations might be greater at 30…”

Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans

“…First, human studies using isolated muscle exercise in acute hypoxia have shown that a reduced arterial hemoglobin saturation (Sa O 2 ), per se, accelerates the rate of accumulation of fatigue metabolites, which in turn exacerbates the development of peripheral muscle fatigue (20, 29 -31, 36, 37, 39, 42). These detrimental effects of reduced Sa O 2 on fatigue metabolite accumulation and the development of peripheral fatigue are supported by studies on isolated animal muscle fibers (21,27). Second, the W b has also been shown to be a major contributor to the development of locomotor muscle fatigue and to limit exercise performance.…”