Decreased shortening velocity and altered myosin isoforms in guinea-pig hypertrophic intestinal smooth muscle.
The aims of this study were to investigate whether hypertrophy of the small intestinal smooth muscle leads to alterations of myosin isoform composition and shortening velocity and whether possible changes correlate with a change in the sensitivity to ADP of shortening velocity in this tissue. A partial occlusion was introduced in the distal part of the ileum of guinea-pigs. After 2 weeks, the part of the small intestine just proximal of the stenosis was hypertrophied (indicated by a significantly increased cross-sectional area). The most proximal part of the small intestine was used as control, thus enabling comparisons between hypertrophic and normal tissue from the same animal. The outer longitudinal layer of the intestinal wall was gently peeled off and used for biochemistry, RT-PCR and mechanical experiments. The desmin/actin ratio was significantly increased following hypertrophy, although myosin and actin expression were similar in control and hypertrophic tissue. In hypertrophic tissue, the myosin heavy chain mRNA with a 21 base pair insert decreased significantly. The composition of the mRNA encoding the myosin essential light chains changed towards more of the basic type (LC17b). No change in the expression of non-muscle myosin heavy chains A and B was detected. The maximal shortening velocity (V(max)) of maximally activated skinned preparations was significantly lower in the hypertrophic tissue (~50 % of control). The sensitivity of V(max) to ADP was increased in the hypertrophic smooth muscle tissue. We conclude that myosin expression is altered following intestinal hypertrophy and that these alterations affect reactions in the cross-bridge interaction, leading to a slower and more economical contractile function.
Löfgren
Mia
M
Department of Physiological Sciences, Lund University, Tornavägen 10, BMC F11, Sweden.
Fagher
Katarina
K
Wede
Oskar Karlsson
OK
Arner
Anders
A
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006984:Hypertrophy; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology* / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000473:pathology* / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D013997:Time Factors
D018994:Myosin Light Chains; D020033:Protein Isoforms; D000244:Adenosine Diphosphate; D018995:Myosin Heavy Chains; D009218:Myosins