Stretch activation is described as a delayed increase in force after an imposed stretch. This process is essential in the flight muscles of many insects and is also observed, to some degree, in mammalian striated muscles. The mechanistic basis for stretch activation remains uncertain, although it appears to involve cooperative activation of the thin filaments (12, 80). The purpose of this study was to address myofibrillar regulatory mechanisms of stretch activation in mammalian striated muscle. For these studies, permeabilized rat slow-twitch and fast-twitch skeletal muscle fibers were mounted between a force transducer and motor, and a slack-re-stretch maneuver was performed over a range of Ca[superscript 2+] activation levels. Following slack-re-stretch there was a stretch activation process that often resulted in a transient force overshoot (P[subscript TO]), which was quantified relative to steady-state isometric force. P[subscript TO] was highly dependent upon Ca[superscript 2+] activation level, and the relative magnitude of P[subscript TO] was greater in slow-twitch fibers than fast-twitch fibers. In both slow-twitch and fast-twitch fibers, force redevelopment involved a fast, Ca[superscript 2+] activation dependent process (k1) and a slower, less activation dependent process (k2). Interestingly, the two processes converged at low levels of Ca[superscript 2+] activation in both fiber types. P[subscript TO] also contained a relaxation phase, which progressively slowed as Ca[superscript 2+] activation levels increased and was more Ca[superscript 2+] activation dependent in slow-twitch fibers. These results suggest that stretch activation may not be solely regulated by the extent of apparent cooperative activation of force due to a higher relative level of stretch activation in the less cooperative slow-twitch skeletal muscle fiber. Next, we investigated an additional potential molecular mechanism by regulating stretch activation in mammalian striated muscle. Along these lines, our lab has previously observed that PKA-induced phosphorylation of cMyBP-C and cTnI elicited a significant increase in transient force overshoot following slack-re-stretch maneuver in permeabilized cardiac myocytes (29). Interestingly, in slow-twitch skeletal muscle fibers MyBP-C but not ssTnI is phosphorylated by PKA (28). We, thus, took advantage of this variation in substrates phosphorylated by PKA to investigate the effects of PKA-induced phosphorylation of MyBP-C on stretch activation in slow-twitch skeletal muscle fibers. Following PKA treatment of skinned slow-twitch skeletal muscle fibers, the magnitude of P[subscript TO] more than doubled, but this only occurred at low levels of Ca[superscript 2+] activation (i.e., [approximately]25% maximal Ca[superscript 2+] activated force). Also, force redevelopment rates were significantly increased over the entire range of Ca[superscript 2+] activation levels following PKA treatment. In a similar manner, force decay rates showed a tendency of being faster following PKA treatment, however, were only statistically significantly faster at 50% Ca[superscript 2+] activation. Overall, these results are consistent with a model whereby stretch transiently increases the number of cross-bridges made available for force generation and PKA phosphorylation of MyBP-C enhances these stretch activation processes.
Erratum: Corrigendum: Defective Acetylcholine Receptor Subunit Switch Precedes Atrophy of Slow-Twitch Skeletal Muscle Fibers Lacking ERK1/2 Kinases in Soleus Muscle
