Skeletal muscle force modulation: length dependent factors

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It is my goal to better understand the fundamental properties of muscles. Active force has been calculated by: peak force - passive force measured at the whole muscle length. We showed that passive force can decrease during a contraction and that active force could be correctly calculated if fiber bundle length is measured using sonomicrography: ultrasound is emitted from a crystal implanted at one end of the fiber bundle and detected by a crystal at the other end. I will investigate properties of muscle that may have previously been misinterpreted due to active force miscalculation. The anesthetized rat medial gastrocnemius muscle will be tested in situ. Individual motor units (defined as any motor neuron and all muscle fibers it innervates) will be activated alone, or in combination with another one with different sized motor units, and at several lengths. Passive force is greater at long lengths, so the miscalculation is greater. I believe the corrected method will give force of two motor units activated together similar to the sum of the two activated separately. There are several reports that lengthening contractions cause the relationship between length and active force to shift to the right. It has been suggested that the shift to longer lengths is caused by increased compliance, but this has not been directly assessed. I will measure compliance, using sonomicrography, and cause damage in muscle, by lengthening contractions or needle piercing and compare the contractile response (including compliance). It is hypothesized that a shift to the right will only be seen when passive force decreases due to the treatment, and active force is calculated in the traditional manner. The rightward shift will not be evident with the corrected method of calculating active force. Muscle responds to increased or decreased use by changing protein synthesis. It is thought that cell signalling mechanisms are sensitive to the force in the muscle, resulting in activation of some key signalling molecules. I propose to measure these, to see if active force, calculated in the correct way is a more sensitive predictor of this than the traditional method. The work that is proposed will advance our fundamental understanding of how muscles function.