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First published online on January 31, 2003.
 Copyright © 2003 by The Physiological Society
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2002.032086v1
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Received September 6, 2002
Accepted after revision January 12, 2003

Isometric force and endurance in skeletal muscle of mice devoid of all known thyroid hormone receptors

Catarina Johansson1, Per Kristian Lunde2, Sten Göthe3, Jan Lännergren1, and H. Westerblad1*

1 Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden
2 Institute for Experimental Medical Research, Ullevaal University Hospital, 0407 Oslo, Norway
3 Department of Cellular and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden

* To whom correspondence should be addressed. E-mail: hakan.westerblad{at}fyfa.ki.se.

The importance of thyroid hormone receptors for isometric force, endurance and content of specific muscle enzymes was studied in isolated slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles in mice deficient in all known subtypes of thyroid hormone receptors (i.e. TR {alpha}1, {beta}1, {beta}2 and {beta}3). The muscle weight was lower in soleus and EDL muscles of TR-deficient (TR{alpha}1-/-{beta}-/-) mice as compared with their wild-type controls. The force per cross-sectional area was not significantly different between TR{alpha}1-/-{beta}-/- and wild-type muscles. Soleus muscles of TR{alpha}1-/-{beta}-/- mice showed increased contraction and relaxation times and the force-frequency relationship was shifted to the left. Soleus muscles of TR{alpha}1-/-{beta}-/- mice were more fatigue resistant than wild-type controls. Protein analysis of TR{alpha}1-/-{beta}-/- soleus muscles showed a marked increase in the slow isoform of the sarcoplasmic reticulum Ca2+ pump (SERCa2), whilst the fast type (SERCa1) was decreased. There was also a major decrease in the {alpha}2-subunit of the Na+-K+ pump in TR{alpha}1-/-{beta}-/- soleus muscles. EDL muscles from TR{alpha}1-/-{beta}-/- and wild-type mice showed no significant difference in contraction and relaxation times, fatigue resistance and protein expression. In conclusion, the present data show changes in contractile characteristics of skeletal muscles of TR{alpha}1-/-{beta}-/- mice similar to those seen in hypothyroidism. We have previously shown that muscles of mice deficient in TR{alpha}1 and TR{beta} display modest changes in muscle function. Thus, in skeletal muscle there seems to be functional overlap between TR{alpha}1 and TR{beta}, so that the lack of one of the receptors to some extent can be compensated for by the presence of the other.




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