Lactic acid restores skeletal muscle force in an in vitro fatigue model: are voltage-gated chloride channels involved?

Abstract

High interstitial K(+) concentration ([K(+)]) has been reported to impede normal propagation of electrical impulses along the muscle cell membrane (sarcolemma) and then also into the transverse tubule system; this is one considered underlying mechanism associated with the development of muscle fatigue. Interestingly, the extracellular buildup of lactic acid, once considered an additional cause for muscle fatigue, was recently shown to have force-restoring effects in such conditions. Specifically, it was proposed that elevated lactic acid (and intracellular acidosis) may lead to inhibition of voltage-gated chloride channels, thereby reestablishing better excitability of the muscle cell sarcolemma. In the present study, using an in vitro muscle contractile experimental setup to study functionally viable rectus abdominis muscle preparations obtained from normal swine, we examined the effects of 20 mM lactic acid and 512 μM 9-anthracenecarboxylic acid (9-AC; a voltage-gated chloride channel blocker) on the force recovery of K(+)-depressed (10 mM K(+)) twitch forces. We observed a similar muscle contractile restoration after both treatments. Interestingly, at elevated [K(+)], myotonia (i.e., hyperexcitability or afterdepolarizations), usually present in skeletal muscle with inherent or induced chloride channel dysfunctions, was not observed in the presence of either lactic acid or 9-AC. In part, these data confirm previous studies showing a force-restoring effect of lactic acid in high-[K(+)] conditions. In addition, we observed similar restorative effects of lactic acid and 9-AC, implicating a beneficial mechanism via voltage-gated chloride channel modulation.

Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function:in vivoinsights from MCT1 haploinsufficient mice

“…Acidosis has been regarded as a potential trigger of skeletal muscle function disturbances (47–49, 52, 85–87). However, this point is largely debated (57–60). Because of these controversies and the pH i alterations expected in MCT1 +/− mice, we believed that investigations of muscle force production and fatigability in this mouse model may be informative.…”

“…The concomitances or correlations reported by several studies conducted in humans provide support for this hypothesis (27, 35, 55, 56). However, several studies, mainly conducted in vitro , disputed the deleterious effect of H + or lactate or both in the impairment of muscle function (57–60). In view of these controversies, the role of H + (and lactate) in muscle function remains unsolved.…”

Comment on: The Effect of Pedal Pump Lymphatic Technique Versus Passive Recovery Following Maximal Exercise: A Randomized Cross-Over Trial

“…During muscle contraction in an intense anaerobic regime, there is an increase in the extracellular potassium concentration, in which increase induces a decrease in the excitability of the sarcolemma [ 6 , 7 ]. Lactic acid, in particular hydrogen, accumulates outside the sarcolemma, protecting and trying to restore the correct membrane voltage, counteracting the inhibiting effect of extracellular potassium [ 7 ]. The relationship between the presence of DOMS and the production of lactic acid is not real: lactic acid does not cause DOMS [ 8 ].…”

Pathophysiologic and anesthetic considerations for patients with myotonia congenita or periodic paralyses

“…Additionally, accumulating interstitial potassium has been proposed as a cause of muscle fatigue . Interestingly, modulations relative to the levels of chloride channel functioning, seems to protect against such potassium‐induced force depression . Further, it should be noted that among other factors (e.g., lactic acid and pH), ATP also seems to be involved in such CLC‐1 modulation .…”