The Journal of Membrane Biology

, Volume 157 , Issue 3 , pp 247 –253

Dihydropyridine Receptor-Ryanodine Receptor Uncoupling in Aged Skeletal Muscle

  • M.  Renganathan
  • M.L.  Messi
  • O.  Delbono

DOI: 10.1007/s002329900233

Cite this article as:
Renganathan, M., Messi, M. & Delbono, O. J. Membrane Biol. (1997) 157: 247. doi:10.1007/s002329900233

Abstract.

The mechanisms underlying skeletal muscle functional impairment and structural changes with advanced age are only partially understood. In the present study, we support and expand our theory about alterations in sarcolemmal excitation-sarcoplasmic reticulum Ca2+ release-contraction uncoupling as a primary skeletal muscle alteration and major determinant of weakness and fatigue in mammalian species including humans. To test the hypothesis that the number of RYR1 (ryanodine receptor) uncoupled to DHPR (dihydropyridine receptor) increases with age, we performed high-affinity ligand binding studies in soleus, extensor digitorum longus (EDL) and in a pool of several skeletal muscles consisting of a mixture of fast- and slow-twitch muscle fibers in middle-aged (14-month) and old (28-months) Fisher 344 Brown Norway F1 hybrids rats. The number of DHPR, RYR1, the coupling between both receptors expressed as the DHPR/RYR1 maximum binding capacity, and their dissociation constant for high-affinity ligands were measured. The DHPR/RYR1 ratio was significantly reduced in the three groups of muscles (pool: 1.03 ± 0.15 and 0.80 ± 0.11, soleus: 0.44 ± 0.12 and 0.26 ± 0.10, and EDL: 0.95 ± 0.14 and 0.68 ± 0.10, for middle-aged and old muscles, respectively). These data support the concept that DHPR-RYR1 uncoupling results in alterations in the voltage-gated sarcoplasmic reticulum Ca2+ release mechanism, decreases in myoplasmic Ca2+ elevation in response to sarcolemmal depolarization, reduced Ca2+ supply to contractile proteins and reduced contraction force with aging.

Key words: Skeletal muscle — Ryanodine receptor — Dihydropyridine receptor — Aging — Excitation-contraction coupling —Soleus muscle —Extensor digitorum longus muscle — Calcium release 

Copyright information

© 1997 Springer-Verlag New York Inc.

Authors and Affiliations

  • M.  Renganathan
    • 1
  • M.L.  Messi
    • 1
  • O.  Delbono
    • 1
  1. 1.Departments of Physiology and Pharmacology and Internal Medicine (Gerontology), The Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USAUS

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