RYR1
Ryanodine receptor 1 (RYR-1) (RyR1) (Skeletal muscle calcium release channel) (Skeletal muscle ryanodine receptor) (Skeletal muscle-type ryanodine receptor) (Type 1 ryanodine receptor) [RYDR]
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The dihydropyridine receptor (DHPR) and ryanodine receptor (RYR1) are needed for excitation-contraction coupling in skeletal muscle. Previous studies from this laboratory have shown DHPR-RYR1 uncoupling in 33-month-old Fischer 344 x Brown Norway F1 (F344BNF1) rats fed ad libitum. The purpose of the present study is to determine whether caloric restriction prevents age-related impairments in skeletal muscle function and expression of DHPR and RyR1. Bundles of soleus and extensor digitorum longus (EDL) were studied from rats fed ad libitum and on 60 percent caloric restriction. Significant differences were found in peak twitch or tetanic tension between the ad libitum and calorie-restricted groups in soleus and EDL muscles. A significant increase in the expression of DHPR and RyR1 was observed in caloric restricted rats. These results show that calorie restriction preserves the mechanical properties of aging hind-limb skeletal muscle and maintains the level of DHPR and RyR1 in aged F344BNF1 rats fed ad libitum.
MeSH Terms
- Aging
- Animals
- Calcium Channels
- Calcium Channels, L-Type
- Crosses, Genetic
- Energy Intake
- Food Deprivation
- Hindlimb
- Muscle Fibers, Skeletal
- Muscle Proteins
- Muscle, Skeletal
- Rats
- Rats, Inbred BN
- Rats, Inbred F344
- Ryanodine Receptor Calcium Release Channel
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.
MeSH Terms
- Aging
- Animals
- Calcium
- Calcium Channels
- Calcium Channels, L-Type
- Muscle Proteins
- Muscle, Skeletal
- Rats
- Rats, Inbred BN
- Rats, Inbred F344
- Receptor Aggregation
- Ryanodine Receptor Calcium Release Channel