Meeting Abstract

P2.171  Saturday, Jan. 5  Breathing with a spring: Exploring the role of titin in respiration MEEHAN, ST*; TAYLOR, KR; NISHIKAWA, KC; Northern Arizona University; Northern Arizona University; Northern Arizona University stm48@nau.edu

Respiration in mammals requires continuous power output and thus a constant energy supply. For that reason, one would expect a strong selective pressure to reduce the energetic cost of respiration. Therefore, the properties of the diaphragm, including muscle stiffness, are expected to impact respiration. The diaphragm muscle in the muscular dystrophy with myositis (MDM) homozygous mutant is about 2-4 times stiffer than in nonmutant mice when the muscle is stretched passively. Mutant MDM mice have a deletion in the N2A region of titin, an integral elastic muscle protein. Nonmutant and mutant mice were filmed with a high-speed digital camera to allow measurement of changes in abdominal width during resting respiration at room temperature. From these measurements, we calculated the respiration rate. The respiration frequency for both mutant and nonmutant mice conformed to allometric predictions and were not significantly different from one another in absolute terms. In addition, the duration of inspiration was similar between nonmutant (77 ms +/- 13 ms) and mutant (80 ms +/- 26 ms) mice. However, the duration of expiration in nonmutants (165 ms +/- 20 ms) was about double the expiratory duration observed for mutants (86 ms +/- 30 ms), meaning that the mutants expired twice as quickly as the nonmutants. The observed doubling of the speed of exhalation in mutants is not difficult to explain since the mutant diaphragm is more than twice as stiff as the nonmutant diaphragm and therefore would be expected to exhibit faster passive recoil. These results provide in vivo support for the idea that mutant muscles are stiffer during the passive phase. Thus, these data indicate that titin stiffness plays an important role in muscle function on the organismal level.