The Influences of L(+)-Lactate and pH on Contractile Performance in Rabbit Glycerinated Skeletal Muscle

Abstract

Prolonged activation of intact skeletal muscle leads to fatigue that is characterized simply by the decrease in peak isometric tension and the maximum shortening velocity (V m ), but the mechanism of fatigue within a muscle fiber has been thought to be complex. The decline in tension generation noted during in vivo fatigue is due to the changes in various factors within a muscle cell, e.g., inadequate activation in excitationcontraction system [1,2], alterations in the calcium sensitivity of the contractile apparatus, and the decrease in the cycling rate of the cross-bridge. The mechanisms of fatigue as mentioned above have been reviewed from different points of view [3][4][5].The production of lactic acid in skeletal muscle has been studied for nearly two centuries, but the influences on exercise or muscular contraction have been subjects of debate [6]. Since the classical works [7][8][9], it has been known that isolated muscles are made to contract until fatigue accumulate lactic acid and that if enough oxygen is present in recovery, the level of lactic acid declines and contractile function is restored [6,8]. Therefore the existence of a close relation between lactic acidosis and the decrease in contractile function has been presumed by physiologists [10,11]. During fatiguing work, the concentration of blood lactate may reach up to 32 mM [12]. The concentration of lactate inside muscle cells is higher than in blood [13], and the maximum concentration may reach up to about 160 mmol kg Ϫ1 dry wt [14], which may mean that the intracellular concentration of lactate is more than 40 mM. More than 99% of lactic acid accumulated in the muscle of exhausted animals may exist in the ionic form at physiological pH as a result of the low pK a (association constant) and may result in a nearly equimolar amount of H + [15]. Actually, an obvious decline in intracellular pH is known to take place during intense muscular work [16], and the intramuscular pH changes from a value of approximately 7 at rest to a value approaching 6 during severe fatigue [3,[16][17][18]. The H ϩ produced in muscle cells can directly affect cross-bridge function and lead to the decline in Ca 2ϩ sensitivity [19][20][21], isometric tension [19,[22][23][24], and shortening velocity [23,24].However, it remains unsettled whether lactate anion Japanese Journal of Physiology, 53, 401-409, 2003 Key words: fatigue, skeletal muscle, lactate, acidosis. Abstract:To know whether L(ϩ)-lactate directly induces the decrease in muscle contractile performance, several parameters of cross-bridge function were measured at various concentrations of lactate and pH in glycerinated rabbit psoas and soleus muscles at three different temperatures (5, 20, 28°C). At all pHs studied (pH 7.0, 6.5, 6.0, and 5.5), isometric tension, unloaded velocity of shortening, and stiffness of a fiber during active and resting state in the presence of 50 mM lactate were not virtually different from those in the absence of lactate, but pH had remarkable effects on these parameters. The activ...

Translocation of molecular chaperones to the titin springs is common in skeletal myopathy patients and affects sarcomere function

“…While reduced pH boosts the aggregation of many sHSP substrates, it also increases the sHSP-mediated protection from aggregation [ 3 , 6 ]. Interestingly, acidosis raises the passive stiffness of skeletal muscles [ 44 ]. Although intracellular pH and oxidative stress were not measured in our biopsy samples, it is reasonable to speculate that exercise increases these parameters more in myopathic than in healthy muscles, which may then cause higher chaperone activity (possibly towards elastic titin) in the diseased cells.…”

Human myocytes are protected from titin aggregation-induced stiffening by small heat shock proteins

“…Bars, 5 µm. and myocardium (Orchard and Kentish, 1990) and can also increase passive tension (Berger et al, 1999;Miyake et al, 2003). In principle, active contraction may be enhanced by sHSP protective effects on actin, troponin, or myosin.…”

“…Contractility of myocytes is strongly affected by intracellular acidosis (Orchard and Kentish, 1990). Studies also suggested that acidosis increases the passive stiffness of the heart (Berger et al, 1999) and of skeletal muscles (Miyake et al, 2003). Intracellular acidosis induced by ischemic stress caused severe diastolic dysfunction in a double-knockout mouse model deficient for B-crystallin and HSPB2 (Golenhofen et al, 2006;Pinz et al, 2008).…”

Human myocytes are protected from titin aggregation-induced stiffening by small heat shock proteins

“…and myocardium (Orchard and Kentish, 1990) and can also increase passive tension (Berger et al, 1999;Miyake et al, 2003). In principle, active contraction may be enhanced by sHSP protective effects on actin, troponin, or myosin.…”

“…Contractility of myocytes is strongly affected by intracellular acidosis (Orchard and Kentish, 1990). Studies also suggested that acidosis increases the passive stiffness of the heart (Berger et al, 1999) and of skeletal muscles (Miyake et al, 2003). Intracellular acidosis induced by ischemic stress caused severe diastolic dysfunction in a double-knockout mouse model deficient for B-crystallin and HSPB2 (Golenhofen et al, 2006;Pinz et al, 2008).…”