Mechanical alterations in smooth muscle from mice lacking desmin.
Mice with a null mutation introduced in the desmin gene were used to study the mechanical role of intermediate filaments in smooth muscle cells. Vas deferens (VD), urinary bladder (UB) and portal vein (PV) preparations were obtained from adult animals lacking desmin (Des -/-) and from age- and weight-matched wild-type animals (Des +/+). Active force per cross-sectional area was decreased in the smooth muscle of the Des -/- compared with Des +/+ mice (VD to 42%; UB to 34%). Quantitative gel electrophoresis suggests a marginally lower cellular content of myosin, but the organization of the contractile apparatus appeared unchanged by electron microscopy. A similar reduction in stress was measured in Des -/- skinned fibres showing that altered activation mechanisms were not involved. The results indicate that the reduced active force is caused by low intrinsic force generation of the contractile filaments or subtle modifications in the coupling between the contractile elements and the cytoskeleton. The relationship between length and passive stress was less steep in the Des -/- samples and a second length force curve after maximal extension revealed a loss of passive stress. The maximal shortening velocity was reduced in Des -/- skinned VD and UB preparations by approximately 25-40%. This was associated with an increased relative content of the basic essential myosin light chain, suggesting that alterations in the contractile system towards a slower, more economical muscle had occurred. PV preparations showed no difference in mechanical properties in Des +/+ and Des -/- animals, a result that was consistent with the predominance of vimentin instead of desmin in this vascular tissue. In conclusion, the results show that, although intermediate filaments in smooth muscle are not required for force generation or maintenance of passive tension, they have a role in cellular transmission of both active and passive force.
Sjuve
R
R
Department of Physiology and Neuroscience, Lund University, Sweden.
Arner
A
A
Li
Z
Z
Mies
B
B
Paulin
D
D
Schmittner
M
M
Small
J V
JV
D000199:Actins / Q000032:analysis; D000818:Animals; D015153:Blotting, Western; D003599:Cytoskeleton / Q000737:chemistry; D003893:Desmin / Q000032:analysis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000737:chemistry* / Q000502:physiology*; D018994:Myosin Light Chains / Q000032:analysis; D011169:Portal Vein / Q000737:chemistry / Q000502:physiology; D013314:Stress, Mechanical; D001743:Urinary Bladder / Q000737:chemistry / Q000502:physiology; D014649:Vas Deferens / Q000737:chemistry / Q000502:physiology
D000199:Actins; D003893:Desmin; D018994:Myosin Light Chains