SALBUTAMOL CHANGES THE MOLECULAR AND MECHANICAL-PROPERTIES OF CANINE SKELETAL-MUSCLE

1. Salbutamol, a beta(2)-agonist, increased the weight of the canine l atissimus dorsi muscle. It also increased fusion frequency, and decrea sed time-to-peak tension, half-relaxation time, and total contraction time. These changes in tn itch times and fusion frequency were associa ted with changes in the levels of proteins expressed in slow- and fast -twitch fil,res. Salbutamol decreased the levels of the slow-twitch ca rdiac isoform of sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA2a) an d phospholamban proteins, and increased the level of tile fast-twitch isoform of sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA1a). 2. Chan ges in the levels of SERCA proteins, particularly SERCA1a, could accou nt for most of the increases in calcium uptake rate observed in homoge nates of muscles from the salbutamol-treated animals and could partial ly account fur the changes in half-relaxation rates: and other twitch times. 3. Changes in the levels of SERCA1a, SERCA2a and phospholamban protein did not always follow changes in the levels of their correspon ding mRNAs. Divergence depended upon the SERCA isoform and muscle. The muscles studied were latissimus dorsi and vastus intermedius. 4. Salb utamol did not change the level of myosin heavy chain (HC)-I isoforms in either muscle, suggesting that it did not increase the proportion o f slow-twitch fibres in these muscles. It did increase the level of HC -IIx and decrease the level of HC-IIa isoforms in the latissimus dorsi . Salbutamol did not produce these effects in the vastus intermedius. It is of particular interest that salbutamol changed the relative leve ls of SERCA proteins in the latissimus dorsi muscle without producing significant changes in the level of HC-I isoform.