Figure 7.

Proposed relationship between breathing, stretch, and gestation age in determining the activation properties of diaphragm fibers in preterm and term fetal sheep. At 127 days gestation, low amplitude FBMs and low neural input result in expression of short titin and little TnC_slow isoform, so that effects of mechanical stretch at this age is minimal – hence little change occurs in the force–pSr curve. At term, maturational changes together with FBMs of increased amplitude result in expression of long titin and greater expression of TnC_slow, so that stretch has greater effects on the lower portion of the force–pSr curve (see dotted line, lower panel). Lower panel: (1) At very low concentration Sr²⁺ binds only to TnC_slow isoforms that have an increased stretch-induced affinity which, if increased at term, allow for greater force production. (2) At term low Sr²⁺ concentration bind to the constitutively expressed TnC_slow isoforms resulting in increased force production. (3) At higher concentrations Sr²⁺ binds all TnC_slow isoforms so that no new cross-bridges (regulated by TnC_slow) are created, producing a plateau in force production. (4) With further increase in concentrations, Sr²⁺ binds to TnC_fast isoforms, creating a second increase in force production.