Bicarbonate‐induced alkalosis augments cellular acetyl group availability and isometric force during the rest‐to‐work transition in canine skeletal muscle

Abstract

Increasing blood bicarbonate content has long been cited as a potential mechanism to improve contractile function. We investigated whether sodium bicarbonate-induced metabolic alkalosis could positively affect force development during the rest-to-work transition in ischaemic skeletal muscle. Secondly, assuming it could, we investigated whether bicarbonate could augment acetyl group availability through the same equilibrium reaction as sodium acetate pre-treatment and whether this underpins, at least in part, its ergogenic effect. Multiple biopsy samples were obtained from the canine gracilis muscle during 5 min of electrically evoked ischaemic Contraction, which enabled the determination of the time course of acetyl group accumulation, substrate utilisation, pyruvate dehydrogenase complex activation and tension development in animals treated with saline (control; n = 6 ) or sodium bicarbonate (n=5). Treatment with bicarbonate elevated acetylcarnitine content above the control level at rest ( P < 0.03, but at no time point during subsequent contraction. The pyruvate dehydrogenase complex was activated following 40 s of contraction in both groups, with no differences existing between treatments at any time point. The requirement for ATP resynthesis from non-oxygen-dependent routes was no different between groups at any time point during contraction. No difference in peak twitch force production existed between groups. However, at 3 min of stimulation, tension development was better maintained in the bicarbonate group (P < 0.05), being -20% greater than control following 5 rnin of contraction (P < 0.05). The results demonstrate, for the first time, that bicarbonate can augment acetyl group availability prior to contraction, independent of pyruvate dehydrogenase complex activation, but cannot influence the requirement for non-oxidative ATP re-synthesis during subsequent contraction. It would appear, therefore, that the bicarbonate-induced improvement in muscle tension development was probably mediated through the metabolic alkalosis and not via the increased availability of acetyl groups within the cell. Experimental Physiologv (2002) 87.4,489498. At the onset of skeletal muscle contraction there is substantial reliance upon ATP re-synthesis from nonoxygen-dependent routes (i.e. ATP and phosphocreatine (PCr) hydrolysis and glycolysis), frequently termed substrate level phosphorylation, to meet the increased energy demand of work, which cannot be met solely via mitochondrial ATP re-synthesis (for review see Greenhaff & Timmons, 1998; Tschakovsky & Hughson, 1999). Although ATP production from substrate level phosphorylation enables rapid rates of ATP turnover to be achieved, it has only a finite capacity and also results in the accumulation of metabolites that are deleterious to muscle function (hydrogen ions, lactate ions and inorganic phosphate)

Acetyl-CoA provision and the acetyl group deficit at the onset of contraction in ischemic canine skeletal muscle

“…4; Ref. 28). Indeed, bicarbonate treatment is known to be associated with an enhancement in muscular performance, especially during periods of high-intensity exercise of short duration (14), as has previously been described within this animal model (28).…”

“…A recent series of studies by our group has demonstrated the existence of metabolic inertia at the onset of contraction (27,28,(33)(34)(35)(36). On the basis of evidence from these studies, we believe that the delay in acetyl-CoA provision at the onset of exercise, which we have termed the "acetyl group deficit" (27), is a principal determinant of the oxygen deficit (27,33,34).…”

“…Classically, the lag in oxidative ATP production and resulting oxygen deficit have been attributed to a lag in muscle blood flow and thereby muscle oxygen delivery, which also follows an approximately exponential time course (21, 30). However, more recently it has been proposed that oxygen availability may not be the sole determinant of the oxygen deficit, at least at submaximal exercise workloads (11,29), such that the delay in mitochondrial energy production must be attributable, at least in part, to a lag in enzyme activation and/or substrate delivery (metabolic inertia) within energy-producing pathways on the initiation of muscular contraction (10,12,18,37).A recent series of studies by our group has demonstrated the existence of metabolic inertia at the onset of contraction (27,28,(33)(34)(35)(36). On the basis of evidence from these studies, we believe that the delay in acetyl-CoA provision at the onset of exercise, which we have termed the "acetyl group deficit" (27), is a principal determinant of the oxygen deficit (27,33,34).…”

Muscular Metabolism in Aged Rats Under Exhaustive Exercise: Effect of a Modified Alkaline Supplementation

“…This is in agreement with an in vitro study proposing that any strategy that increases the mitochondrial availability of acetyl groups and concomitantly increases blood bicarbonate content may improve the maintenance of contractile function. 2 This may also explain the observed increase of acetylcarnitine, 5 which is known to fluctuate during contraction according to acetyl-CoA availability. In agreement, Hollidge-Horvat et al 6 have reported a trend increase of acetyl-carnitine content in human skeletal muscle following sodium bicar-bonate ingestion.…”

“…Another mechanism by which bicarbonate may improve contractile function is by increasing the availability of acetyl-CoA towards the tricarboxylic acid cycle. 2 The aim of this study was to test whether a modified alkalizing supplementation could improve muscular metabolism and adaptation to exhaustive exercise in aged rats by examining either the gastrocnemius (fast muscle related to instantaneous force) and the soleus (slow muscle related to endurance).…”