Figure 1.

Force-frequency (A) and force-calcium (B) relationships. A. There is a sigmoid relationship between stimulation frequency and force generated by a muscle. Although the shape of the relationship is similar in vivo and in vitro and between fiber types, the precise values for the stimulation frequencies vary and are an approximation in this figure. The solid line illustrates the force-frequency relationship for a nonfatigued muscle. The dashed line illustrates the characteristic decline in force at low activation frequencies that occurs during low-frequency fatigue. B. The sigmoid relationship between calcium and force can give rise to the shift in the force-frequency curve as illustrated in (A). A uniform decline in the intracellular calcium (Ca²⁺) transient at all stimulation frequencies will cause force to fall along sigmoid curve as illustrated by the solid arrows. At high activation frequencies, the decline in Ca²⁺ occurs along the plateau of the curve and will have little effect of force; compare high frequency solid (control) and dashed (fatigue) arrows. In contrast, a similar relative decline in Ca²⁺ release at lower activation frequencies will fall along the steep part of the relationship and will cause a substantial decline in force (compare low frequency solid and dashed arrows).