Effects of chronic low-frequency stimulation on Ca2+-regulatory membrane proteins in rabbit fast muscle

Since chronic low-frequency stimulation of fast-twitch muscle fibers has a profound effect on all major functional elements of skeletal muscle, we ana lyzed the potential changes in the levels of Ca2+-regulatory membrane prote ins during fast-to-slow transformation. In this study we show that, in addi tion to isoform-switching in myosin heavy chains, electrostimulation trigge rs a decline in fast isoforms and an increase in slow/cardiac isoforms of C a2+-ATPase and calsequestrin. The levels of excitation-contraction coupling elements, such as the ryanodine receptor, the dihydropyridine receptor, tr iadin and sarcalumenin, decreased sharply following stimulation. In contras t, levels of Na+/K+-ATPase and calreticulin increased in the microsomal fra ction. Crosslinking studies have revealed that in normal and stimulated mus cle the Ca2+-ATPase isoforms exist predominantly as oligomeric structures, and that the central elements of excitation-contraction coupling also form large triad complexes. Changes in the levels and pattern of isoform express ion of the muscle membrane proteins studied here suggest that these; bioche mical alterations reflect molecular adaptations to changed demands in ion h omeostasis and signal transduction in muscle that exhibits enhanced contrac tile activity. Overall, these findings support the physiological concept th at there are muscle fiber-type specific differences in the fine-tuning of t he excitation-contraction-relaxation cycle, as well as the idea that mature skeletal muscle fibers exhibit a high degree of plasticity.