INDUCTION OF MOLECULAR AND MECHANICAL TRANSFORMATIONS IN CANINE SKELETAL-MUSCLE BY CHRONIC NEUROMUSCULAR STIMULATION

The canine latissimus dorsi was stimulated at 1 Hz via the thoracodors al nerve for 70 days. Seven days of muscle stimulation caused muscle m ass, fibre cross-sectional areas, and tetanic tensions to decrease. Fo urteen days of stimulation produced marked decreases in Ca2+-uptake ra tes in a membrane fraction containing sarcoplasmic reticulum. At this time there was a decline in fusion frequency, but no statistically sig nificant changes in time-to-peak tension, total contraction times, or half-relaxation times. With 42 days of stimulation a switch from the f ast-twitch to the slow-twitch phenotype was indicated by elevations in the levels of expression of the slow-twitch isoform of sarco(endo)pla smic reticulum Ca2+-ATPase and myosin heavy chain-1, and increases in half-relaxation times, total contraction times and time-to-peak tensio ns. Decreases in muscle shortening velocity correlated negatively with increases in myosin heavy chain-1 levels. Up-regulation of the slow-t witch isoform of sarco(endo)plasmic reticulum Ca2+-ATPase protein posi tively correlated with increases in half-relaxation times. The changes in the slow-twitch isoform of sarco(endo)plasmic reticulum Ca2+-ATPas e and myosin heavy chain-I levels indicated coordinate expression of t hese two proteins in chronically stimulated muscles.