O. Delbono et al., EXCITATION CALCIUM-RELEASE UNCOUPLING IN AGED SINGLE HUMAN SKELETAL-MUSCLE FIBERS, The Journal of membrane biology, 148(3), 1995, pp. 211-222
The biological mechanisms underlying decline in muscle power and fatig
ue with age are not completely understood. The contribution of alterat
ions in the excitation-calcium release coupling in single muscle fiber
s was explored in this work. Single muscle fibers were voltage-clamped
using the double Vaseline gap technique. The samples were obtained by
needle biopsy of the vastus lateralis (quadriceps) from 9 young (25-3
5 years; 25.9 +/- 9.1; 5 female and 4 male) and 11 old subjects (65-75
years; 70.5 +/- 2.3; 6 f, 5 m), Data were obtained from 36 and 39 fib
ers from young and old subjects, respectively. Subjects included in th
is study had similar physical activity. Denervated and slow-twitch mus
cle fibers were excluded from this study. A significant reduction of m
aximum charge movement (Q(max)) and DHP-sensitive Ca current were reco
rded in muscle fibers from the 65-75 group. Q(max) values were 7.6 +/-
0.9 and 3.2 +/- 0.3 nC/mu F for young and old muscle fibers, respecti
vely (P < 0.01). No evidences of charge inactivation or interconversio
n (charge 1 to charge 2) were found. The peak Ca current was (-)4.7 +/
- 0.08 and (-)2,15 +/- 0.11 mu A/mu F for young and old fibers, respec
tively (P < 0.01). The peak calcium transient studied with mag-fura-a
(400 mu M) was 6.3 +/- 0.4 mu M and 4.2 +/- 0.3 mu M for young and old
muscle fibers, respectively. Caffeine (0.5 mM) induced potentiation o
f the peak calcium transient in both groups. The decrease in the volta
ge-/Ca-dependent Ca release ratio in old fibers (0.18 +/- 0.02) compar
ed to young fibers (0.47 +/- 0.03) (P < 0.01), was recorded in the abs
ence of sarcoplasmic reticulum calcium depletion. These data support a
significant reduction of the amount of Ca available for triggering me
chanical responses in aged skeletal muscle and, the reduction of Ca re
lease is due to DHPR-ryanodine receptor uncoupling in fast-twitch fibe
rs. These alterations can account, at least partially far the skeletal
muscle function impairment associated with aging.