<doi>10.1085/jgp.200509483</doi><aid>200509483</aid>Functions of Stretch Activation in Heart Muscle

Correspondence to Kenneth B. Campbell: [email protected] Stretch activation is an intrinsic length-sensing mechanism that allows muscle to function with an autonomous regulation that reduces reliance on extrinsic regulatory systems. This autonomous regulation is most dramatic in asynchronous insect fl ight muscle and gives rise to wing beat frequencies that exceed the frequency capacity of neural motor control systems. Stretch activation in insect fl ight muscle allows the contractile features of the fl ight muscle to be matched and tuned to the wingthorax-aerodynamic load to ensure proper muscle contraction frequency and effort for fl ight (Pringle, 1977); a role for which intrinsic autonomous regulation is especially suited. In stretch-sensitive insect fl ight muscles, neurally controlled intracellular calcium plays a permissive role (it needs to be present at adequate levels to allow the intrinsic stretch activation mechanisms to operate) but it is not the dominant player in force generation or in work production. That role belongs to stretch itself, which activates the myofi lament system in such a way (i.e., with appropriate phase delay) to generate force and perform rhythmic work. The function of stretch activation is less obvious in muscles, such as cardiac muscle, that rely heavily on rising and falling intracellular calcium to modulate force generation. Although stretch activation has been demonstrated in cardiac muscle (Steiger, 1971, 1977; Vemuri et. al., 1999), intracellular activator calcium is the primary determinant of force-generating capacity. However, two unique features of cardiac muscle function suggest that stretch activation could be important: (1) the rhythmic nature of cardiac muscle contraction begs a functional analogy for stretch activation in heart muscle with stretch activation in insect fl ight muscle; and (2) the steep length–tension relationship in cardiac muscle (relative to skeletal muscle, where stretch activation is much less pronounced) is necessary for the valuable function that the heart gains from the Frank-Starling relationship (Allen and Kentish, 1985). It is likely that stretch activation contributes signifi cantly to this steepness. Thus, the relative contribution of stretch activation and calcium activation to cardiac muscle function is an important issue that remains largely unresolved.