Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3

Skeletal muscle expresses at least two isoforms of the calcium release chan nel in the sarcoplasmic reticulum (RyR1 and RyR3). Whereas the function of RyR1 is well defined, the physiological significance of RyR3 is unclear. So me authors have suggested that RyR3 participates in excitation-contraction coupling and that RyR3 may specifically confer resistance to fatigue. To te st this hypothesis, we measured contractile function of diaphragm strips fr om adult RyR3-deficient mice (exon 2-targeted mutation) and their heterozyg ous and wild-type littermates. In unfatigued diaphragm, there were no diffe rences in isometric contractile properties (twitch characteristics, force-f requency relationships, maximal force) among the three groups. Our fatigue protocol (30 Hz, 0.25 duty cycle, 37 degrees C) depressed force to 25% of t he initial force; however, lack of RyR3 did not accelerate the decline in f orce production. The force-frequency relationship was shifted to higher fre quencies and was depressed in fatigued diaphragm; lack of RyR3 did not exag gerate these changes. We therefore provide evidence that RyR3 deficiency do es not alter contractile function of adult muscle before, during, or after fatigue.