Active and passive tension interact to promote Akt signaling with muscle contraction

Purpose: The extent to which factors associated with muscle contraction activate Akt remains unclear. This study examined the influences of mechanical (active and passive tension), neural (activation frequency), and metabolic (glycogen depletion) factors on Akt activation during in situ contractions. Methods: Muscle length was modified to produce comparable active contractile forces in three protocols, despite a twofold difference in stimulation frequency (15 vs 30 Hz); a fourth protocol used 30-Hz stimulation at optimal length to produce greater active forces. Two protocols were performed at optimal length, using 15- or 30-Hz stimulation (15 Hz(opt) and 30 Hz(opt) respectively). Two other protocols used 30-Hz stimulation at shortened or lengthened positions (30 HZ(sub) and 30 HZ(supr)a respectively). Results: The principal finding was that the 30-Hz(opt) protocol induced significantly greater Akt phosphorylation (approximately threefold relative to control) than did the other protocols, suggesting that activation of this signaling pathway is most sensitive to active tension. This result could not be attributed to differences in glycogen depletion, stimulation frequency, or fatigue. Despite producing the lowest force-time integral, the 30-Hz(supra) protocol, which had the greatest passive tension, exhibited a greater degree of Akt phosphorylation than did the 15-Hz(opt) and 30-Hz(sub) protocols. Although these differences were not significant, they suggest a possible secondary role for passive tension, which may interact with active tension in activating the Akt signaling pathway. Conclusion: Akt activation seems more sensitive to active contractile tension than to passive tension. Activation frequency seems to play no role in the phosphorylation of Akt.