Skeletal muscle fatigue: pH effects on contractile function and excitation-contraction coupling in single cells

Shannon T Knuth, Marquette University


High-frequency skeletal muscle contraction results in muscle fatigue and a decrease in intracellular pH from pH 7.0 to values as low as pH 6.2. Fatigue-induced alterations and recovery of muscle contractile properties correlate with the recovery of intracellular pH (pHi) and suggest that increased H+ is causative in fatigue. The purpose of this dissertation was to determine the effect of acidosis on the cellular properties of muscle contraction. Specifically, investigations determined pH effects on sarcoplasmic reticulum (SR) Ca2+ transients and the temperature dependency of pH induced alterations in contractile function. The transient release of Ca2+ from the SR is the result of muscle excitation-contraction (E-C) coupling and may be inhibited by low pH. This investigation used voltage clamped cut fiber preparation and microspectrophotometry of the Ca2+ binding dye, AP III to examine the effect of pH 6.2 on SR Ca2+ transients. Low pH (pH 6.2) increased the amplitude of the Ca2+ transient indicating that H+ ions may displace Ca2+ from intracellular binding sites (such as troponin C) and account for the reduction in force observed in muscle fatigue. However, additional evidence suggests that the Ca2+ and pH buffers were independently effected by low pH and these interactions may account for the results observed. The second investigation focused on pH effects on the cross-bridge cycle. A reduction in pH from 7.0 to 6.2 at 15°C decreased skinned fiber tension (Po), shortening velocity (Vo), and peak power, 32%, 19%, and 23%, respectively in type I fibers of the soleus. In comparison at 30°C the effect of low pH on Po was attenuated ([Special characters omitted.] 6%), while the change in Vo and peak power was magnified as they decreased 24%, and 30% respectively. A similar response was observed in the type I and IIa fibers of the red gastrocnemius. These results indicate that a decrease in pH similar to that observed in fatigued cells effects the cross-bridge cycle at physiological muscle temperature and reduces the peak power production of single muscle cells. The increase in protons is thought to directly effect cross-bridge transition into the high force state causing a reduction in Po which is attenuated at high temperature. The slowing of single fiber shortening velocity may be due to a decrease in myofilament lattice spacing caused by excess hydrogen ions and magnified at high temperature.

Recommended Citation

Knuth, Shannon T, "Skeletal muscle fatigue: pH effects on contractile function and excitation-contraction coupling in single cells" (2000). Dissertations (1962 - 2010) Access via Proquest Digital Dissertations. AAI9977733.