Denervation produces different single fiber phenotypes in fast- and slow-twitch hindlimb muscles of the rat

• Published in: American Journal of Physiology: Cell Physiology 2006-09, Vol.291 (3), p.518-528
• Main Authors: Patterson, M. F, Stephenson, G. M. M, Stephenson, D. G
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Calcium - metabolism; Cells; Enzymes; Hindlimb - innervation; Hydrogen sulfide; Male; Muscle Contraction - physiology; Muscle Denervation; Muscle Fibers, Fast-Twitch - chemistry; Muscle Fibers, Fast-Twitch - physiology; Muscle Fibers, Slow-Twitch - chemistry; Muscle Fibers, Slow-Twitch - physiology; Muscle, Skeletal - innervation; Myosin Heavy Chains - analysis; Pancreas; Protein Isoforms - analysis; Rats; Rats, Long-Evans; Sciatic Nerve - surgery; Strontium - metabolism
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00013.2006

1 Department of Zoology, La Trobe University, Melbourne; and 2 Muscle Cell Biochemistry Laboratory, School of Biomedical Sciences, Victoria University, Melbourne, Victoria, Australia Submitted 12 January 2006 ; accepted in final form 31 March 2006 Using a single, mechanically skinned fiber approach, we tested the hypothesis that denervation (0 to 50 days) of skeletal muscles that do not overlap in fiber type composition [extensor digitorum longus (EDL) and soleus (SOL) muscles of Long-Evans hooded rats] leads to development of different fiber phenotypes. Denervation (50 day) was accompanied by 1 ) a marked increase in the proportion of hybrid IIB/D fibers (EDL) and I/IIA fibers (SOL) from 30% to >75% in both muscles, and a corresponding decrease in the proportion of pure fibers expressing only one myosin heavy chain (MHC) isoform; 2 ) complex muscle- and fiber-type specific changes in sarcoplasmic reticulum Ca 2+ -loading level at physiological pCa 7.1, with EDL fibers displaying more consistent changes than SOL fibers; 3 ) decrease by 50% in specific force of all fiber types; 4 ) decrease in sensitivity to Ca 2+ , particularly for SOL fibers (by 40%); 5 ) decrease in the maximum steepness of the force-pCa curves, particularly for the hybrid I/IIA SOL fibers (by 35%); and 6 ) increased occurrence of biphasic behavior with respect to Sr 2+ activation in SOL fibers, indicating the presence of both slow and fast troponin C isoforms. No fiber types common to the two muscles were detected at any time points ( day 7 , 21 , and 50 ) after denervation. The results provide strong evidence that not only neural factors, but also the intrinsic properties of a muscle fiber, influence the structural and functional properties of a particular muscle cell and explain important functional changes induced by denervation at both whole muscle and single cell levels. mechanically skinned fibers; myosin heavy chain isoforms; lineage; sarcoplasmic reticulum; Ca 2+ ; Sr 2+ sensitivity; Long-Evans hooded rat Address for reprint requests and other correspondence: D. G. Stephenson, Dept. of Zoology, La Trobe Univ., Kingsbury Dr., Melbourne, Victoria, 3086, Australia (e-mail: george.stephenson{at}latrobe.edu.au )