Effects of fatiguing stimulation on intracellular Na+ and K+ in frog skeletal muscle

The purpose of this study was to describe the alterations in the intracellular concentrations of sodium ([Na+](i)) and potassium ([K+](i)) and the membrane potential (E(m)) as a result of fatiguing stimulation of the frog semitendinosus muscle and to relate these changes to the alterations in the sarcolemma action potential and force-generating ability of the muscle. [Na+](i) and [K+](i) were measured by using ion-selective microelectrodes. Before stimulation (100-ms trains at 150 Hz, 1 stimulus/s for 5 min), [Na+](i), [K+](i), and E(m) were 16 +/- 1 mM, 142 +/- 5 mM, and -83 +/- 1 mV, respectively. As a result of stimulation, [Na+](i) rose to 49 +/- 6 mM and recovered to 16 +/- 2 mM with a time constant (tau) of 70 s .[K+](i) fell to 97 +/- 8 mM as a result of stimulation, then recovered to 148 +/- 5 mM with tau = 56 s. E(m) depolarized to -74 +/- 3 mV then recovered to -83 +/- 2 mV with tau = 53 s. The Na+/K+ permeability ratio of the resting membrane fell 3%, whereas at the peak of the action potential the permeability ratio fell 38%. A previous study using the same muscle and stimulation protocol showed force to recover with a fast initial phase (similar to 2 min) and a much slower second phase (similar to 50 min). The recovery of [Na+](i), [K+](i), and E(m) was similar to the fast phase of force recovery; thus the altered Na+ and K+ concentration gradient across the sarcolemma and t-tubular membrane may contribute to this component of fatigue. The possible fatigue mechanisms induced by the altered ionic gradients include 1) complete block of the action potential propagation; 2) depolarization-induced inactivation of t-tubular charge movement; and 3) a reduced magnitude of the t-tubular charge due to the lower action potential spike potential.