科学家提出了一个机制，也许能解释肌肉中的乳酸积累帮助抵御肌肉疲劳这个非传统的观念。当身体消耗和缺氧导致肌肉进入一个不用氧的能量生产系统时，肌肉细胞产生乳酸。科学家报告说，乳酸生产所带来的不断增加的酸性帮助肌肉保持它们的电应激性和收缩能力。增加的酸性似乎降低了休息肌肉中的一个机制，这个机制用氯离子来防止自发收缩。这个丹麦和澳大利亚的小组用大鼠肌肉纤维做试验，通过改变纤维内部的条件，观察了酸性对力响应的影响。在一篇相关的研究评述中，David Allen描述了肌肉疲乏研究中乳酸的历史。
Lactic Acid--The Latest Performance-Enhancing Drug
Runners routinely blame their weak and aching muscles on the accumulation of lactic acid. But not so fast, say Allen and Westerblad in their Perspective. They discuss a study (Pedersen et al.) revealing that lactic acid accumulation can, in fact, be beneficial by helping to restore force to weakened muscles. By altering the activity of chloride ion channels, lactic acid may actually boost the generation of action potentials and, hence, muscle activity even as the muscles begin to fatigue.
全文下载：
点击浏览该文件
Intracellular Acidosis Enhances the Excitability of Working Muscle
Intracellular acidification of skeletal muscles is commonly thought to contribute to muscle fatigue. However, intracellular acidosis also acts to preserve muscle excitability when muscles become depolarized, which occurs with working muscles. Here, we show that this process may be mediated by decreased chloride permeability, which enables action potentials to still be propagated along the internal network of tubules in a muscle fiber (the T system) despite muscle depolarization. These results implicate chloride ion channels in muscle function and emphasize that intracellular acidosis of muscle has protective effects during muscle fatigue.
Fig. 1. Modes of activation of mechanically skinned muscle fibers. The force responses (right) were all obtained with the same preparation. Calibration bars for all force responses: vertical, 0.3 mN, and horizontal, 5 s. Upward-pointing arrows indicate time of activation and downward-pointing arrows indicate subsequent relaxation in a heavily buffered EGTA solution ([Ca2+] < 1 nM). (A) Electrical stimulation initiates APs in the sealed T system. Shown is a tetanic contraction at 25 Hz stimulation with square pulses of 2-ms duration for 1s and field strength of 70 V/cm in a standard K-hexamethylene-diamine-tetraacetate (KHDTA) solution with Cl– (10, 11, 21). (B) Depolarization of the T system (by replacing all K+ in the solution with Na+) activates VSs independently of APs in the T system. The force response resulted from transfer of the preparation from a standard K-HDTA solution to depolarizing Na-HDTA solution (5). (C) Direct activation of SR Ca2+-release channels, causing Ca2+ release from the SR, and force production when free [Mg2+] in the solutions was lowered from 1 mM to 0.015 mM (5). (D) Direct activation of the contractile apparatus in Ca2+-buffered solutions (5, 10, 11, 21). The preparation was transferred from the standard K-HDTA solution ([Ca2+] = 100 nM) to heavily buffered Ca-EGTA solution ([Ca2+] = 30 µM).
Fig. 2. Effect of pH and T system depolarization on force responses induced by direct VS activation (A and B) or tetanic stimulation at 25 Hz (C and D) in the presence of Cl– in mechanically skinned fibers at 25° ± 2°C. EDL muscles of rats [Long Evans Hooded, 6-month-old males, killed by halothane overdose (5)] were placed in paraffin oil and skinned fibers were prepared as described (5, 10, 11, 21). Fibers were attached to a sensitive force transducer and bathed in solutions mimicking the myoplasmic environment (5, 10, 11, 21). The K-HDTA standard solution at pH = 7.10 contained 126 mM K+, 17 mM methylsulfate, 3 mM Cl–, 40 mM Na+, 40 mM HDTA2–, 1 mM Mg2+ (free), 8 mM adenosine triphosphate, 10 mM creatine phosphate, 90 mM Hepes buffer, 0.05 mM Bapta [(1,2-bis0-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid], and 100 nM Ca2+. The K-HDTA standard solution at pH = 6.60 was identical to the K-HDTA solution at pH = 7.10 with respect to all ions except that it contained 9 mM Pipes and Hepes was reduced to 80 mM to maintain osmotic balance (295 ± 2 mmol/kg). In solutions with decreased [K+]i, K+ was replaced with NH4+ and methylsulfate with Cl– to maintain constant [K+]i [Cl–]i product. (A and C) Representative force traces from two individual fibers. Bars under traces represent the duration of stimulation [ion substitution for (A) and 25-Hz tetanic stimulation for (C)]. The voltage sensor–activated force response at pH = 6.6 (75 mM K+) is only slightly smaller than the corresponding response at pH = 7.1, with the difference entirely due to the decrease in maximum Ca2+-activated force at pH = 6.6, which was smaller by 19 ± 9% (n = 49) compared with that at pH = 7.1. The horizontal lines in (A) and (C) indicate the maximum Ca2+-activated force generated at pH = 7.1 and pH = 6.6 in buffered Ca-EGTA solutions ([Ca2+] = 30 µM) in which HDTA2– was replaced by Ca-EGTA2–. Calibration bars: vertical, 0.1 mN, and horizontal, 5 s. Membrane potentialin the various [K+]i solutions was calculated from the Goldman-Hodgkin-Katz equation (14). For each data point n was from 5 to 8.
Fig. 3. Effect of pH and T system depolarization on force responses at 25° ± 2°C induced by direct VS activation (A and B) or tetanic stimulation at 25 Hz (C and D) in the absence of Cl–. Before skinning, the muscles were equilibrated for 30 min in Cl–-free Ringer's solution containing 65 mM Hepes, 1.2 mM Ca2+, 115 mM sodium methylsulfate, 4 mM K+, 1.2 mM phosphate, and 5 mM glucose. NaOH was used to bring pH to 7.4. All intracellular solutions had the same composition as the solutions described in the legend of Fig. 2 except Cl– was replaced with methylsulfate. Membrane potential in the various [K+]i solutions was calculated as described (Fig. 2). (A and C) Representative force traces from two individual fibers. Bars under traces represent the duration of stimulation. (C) The horizontal lines indicate the maximum Ca2+-activated force at pH values of 7.1 and 6.6 in heavily buffered Ca-EGTA solutions (Fig. 2). Calibration bars: vertical 0.1 mN, horizontal 5 s. The broken lines shown in (D) represent the curves from Fig. 2D.
Fig. 4. Effect of pH on Cl– permeability in the T system. Representative VS activated force responses in a mechanically skinned fiber equilibrated in solutions of different [K+]i and [Cl–]i at pH values of 7.1 and 6.6. Calibration bars: vertical, 0.1 mN; horizontal, 5 s. At constant [K+]i[Cl]i product, the membrane potentials were calculated as described in text, and at 80 K+ and 20 Cl– the membrane potential was estimated from Fig. 2B.
