EFFECT OF INTRACELLULAR AND EXTRACELLULAR ION CHANGES ON E-C COUPLINGAND SKELETAL-MUSCLE FATIGUE

The causative factors in muscle fatigue are multiple. and vary dependi ng on the intensity and duration of the exercise, the fibre type compo sition of the muscle. and the individual's degree of fitness. Regardle ss of the aetiology. fatigue is characterized by the inability to main tain the required power output. and the decline in power can be attrib uted to a reduced force and velocity. Following high-intensity exercis e. peak force has been shown to recover biphasically with an initial r apid (2 min) recovery followed by a slower (50 min) return to the pre- fatigued condition. The resting membrane potential depolarizes by 10-1 5 mV, while the action potential overshoot declines by a similar magni tude. Following high-frequency stimulation of the frog semitendinous m uscle. we observed intracellular potassium [K+](i) decrease from 142 /- 5 to 97 +/- 8 mM, while sodium [Na+](i) rose from 16 +/- 1 to 49 +/ - 6 mM. The [K+](i) loss was similar to that observed in fatigued mous e and human skeletal muscle. which suggests that there may be a limit to which [K+](i) can decrease before the associated depolarization beg ins to limit the action potential frequency. Fibre depolarization to - 60 mV (a value observed in some cells) caused a significant reduction in the t-tubular charge movement, and the extent of the decline was in versely related to the concentration of extracellular Ca2+. A decrease in intracellular pH (pH(i)) to 6.0 was observed. and it has been sugg ested by some that low pH may disrupt E-C coupling by directly inhibit ing the SR Ca2+ release channel. However. Lamb at al. (1992) observed that low pH had no effect on Ca2+ release, and we found low pH(i) to h ave no effect on t-tubular charge movement (Q) or the Q vs. V-m relati onship. The Ca2+ released from the SR plays three important roles in t he regulation of E-C coupling. As Ca2+ rises. it binds to the inner su rface of the t-tubular charge sensor to increase charge (Q(y)) and thu s Ca2+ release, it opens SR Ca2+ channels that are not voltage-regulat ed. and as [Ca2+](i) increases further it feeds back to close the same channels. The late stages of fatigue have been shown to be in part ca used by a reduced SR Ca2+ release. The exact cause of the reduced rele ase is unknown. but the mechanism appears to involve a direct inhibiti on of the SR Ca2+ channel.