Effects of low cell pH and elevated inorganic phosphate on the pCa-force relationship in single muscle fibers at near-physiological temperatures.
Intense muscle contraction induces high rates of ATP hydrolysis with resulting increases in Pi, H(+), and ADP, factors thought to induce fatigue by interfering with steps in the cross-bridge cycle. Force inhibition is less at physiological temperatures; thus the role of low pH in fatigue has been questioned. Effects of pH 6.2 and collective effects with 30 mM Pi on the pCa-force relationship were assessed in skinned fast and slow rat skeletal muscle fibers at 15 and 30°C. At 30°C, pH 6.2 + 30 mM Pi significantly depressed peak force in all fiber types, with the greatest effect in type IIx fibers. Across fiber types, Ca(2+) sensitivity was depressed by low pH and low pH + high Pi, with the greater effect at 30°C. For type IIx fibers at 30°C, half-maximal activation (pCa50) was 5.36 at pH 6.2 (no added Pi) and 4.98 at pH 6.2 + 30 mM Pi compared with 6.58 in the control condition (pH 7, no added Pi). At 30°C, n2, reflective of thick filament cooperativity, was unchanged by low cell pH but was depressed from 5.02 to 2.46 in type IIx fibers with pH 6.2 + 30 mM Pi. With acidosis, activation thresholds of all fiber types required higher free Ca(2+) at 15 and 30°C. With the exception of type IIx fibers, the Ca(2+) required to reach activation threshold increased further with added Pi. In conclusion, it is clear that fatigue-inducing effects of low cell pH and elevated Pi at near-physiological temperatures are substantial.
Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin.
Cassandra R
CR
Nelson
Robert H
RH
Fitts
D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001831:Body Temperature; D020013:Calcium Signaling; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D009119:Muscle Contraction; D018763:Muscle Fatigue; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D053580:Muscle Strength; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010710:Phosphates
cross-bridge cycle; fatigue; myofilament calcium sensitivity