Regulation of dihydropyridine receptor gene expression in mouse skeletal muscles by stretch and disuse.
This study examined dihydropyridine receptor (DHPR) gene expression in mouse skeletal muscles during physiological adaptations to disuse. Disuse was produced by three in vivo models-denervation, tenotomy, and immobilization-and DHPR alpha1s mRNA was measured by quantitative Northern blot. After 14-day simultaneous denervation of the soleus (Sol), tibialis anterior (TA), extensor digitorum longus (EDL), and gastrocnemius (Gastr) muscles by sciatic nerve section, DHPR mRNA increased preferentially in the Sol and TA (+1.6-fold), whereas it increased in the EDL (+1.6-fold) and TA (+1.8-fold) after selective denervation of these muscles by peroneal nerve section. It declined in all muscles (-1.3- to -2.6-fold) after 14-day tenotomy, which preserves nerve input but removes mechanical tension. Atrophy was comparable in denervated and tenotomized muscles. These results suggest that factor(s) in addition to inactivity per se, muscle phenotype, or associated atrophy can regulate DHPR gene expression. To test the contribution of passive tension to this regulation, we subjected the same muscles to disuse by limb immobilization in a maximally dorsiflexed position. DHPR alpha1s mRNA increased in the stretched muscles (Sol, +2.3-fold; Gastr, +1.5-fold) and decreased in the shortened muscles (TA, -1.4-fold; EDL, -1.3-fold). The effect of stretch was confirmed in vitro. DHPR protein did not change significantly after 4-day immobilization, suggesting that additional levels of regulation may exist. These results demonstrate that DHPR alpha1s gene expression is regulated as an integral part of the adaptive response of skeletal muscles to disuse in both slow- and fast-twitch muscles and identify passive tension as an important signal for its regulation in vivo.
Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio 45267-0576, USA.
Tatiana L
TL
Radzyukevich
Judith A
JA
Heiny
D000222:Adaptation, Physiological; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D019417:Hindlimb Suspension; D051379:Mice; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000502:physiology*; D020966:Muscular Disorders, Atrophic / Q000503:physiopathology; D009924:Organ Culture Techniques; D012333:RNA, Messenger; D013314:Stress, Mechanical; D013710:Tendons / Q000601:surgery
D020746:Calcium Channels, L-Type; D012333:RNA, Messenger