1. Salbutamol, a fl2-agonist, increased the weight of the canine latissimus dorsi muscle. It also increased fusion frequency, and decreased time-to-peak tension, half-relaxation time, and total contraction time. These changes in twitch times and fusion frequency were associated with changes in the levels of proteins expressed in slow-and fast-twitch fibres. Salbutamol decreased the levels of the slow-twitch cardiac isoform of sarco-/endoplasmic reticulum Ca2P-ATPase (SERCA2a) and phospholamban proteins, and increased the level of the fast-twitch isoform of sarco-/endoplasmic reticulum Ca2+-ATPase (SERCAla).2. Changes in the levels of SERCA proteins, particularly SERCAla, could account for most of the increases in calcium uptake rate observed in homogenates of muscles from the salbutamol-treated animals and could partially account for the changes in half-relaxation rates and other twitch times.3. Changes in the levels of SERCAla, SERCA2a and phospholamban protein did not always follow changes in the levels of their corresponding mRNAs. Divergence depended upon the SERCA isoform and muscle. The muscles studied were latissimus dorsi and vastus intermedius. 4. Salbutamol did not change the level of myosin heavy chain (HC)-I isoforms in either muscle, suggesting that it did not increase the proportion of 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 levels of SERCA proteins in the latissimus dorsi muscle without producing significant changes in the level of HC-I isoform.

1. The effect of simultaneous application of chronic muscle stimulation and salbutamol on the expression of mRNAs and proteins normally expressed by fast- or slow-twitch fibres was followed and the effects of changes in protein expression on mechanical performance were evaluated. Chronic low-frequency stimulation increased the myosin heavy chain (HC)-I level in the canine latissimus dorsi muscle and simultaneous administration of salbutamol partially blocked this change. Associated with the increase in HC-I level was a decrease in the velocity of shortening at zero load, VMAX. The change in VMAX was partially blocked by salbutamol. 2. Chronic low-frequency stimulation increased the levels of slow-twitch cardiac isoform sarco-/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban mRNA, and SERCA2a and phospholamban protein expression. These changes were associated with an increase in time-to-peak tension and a decrease in fusion frequency. Simultaneous administration of salbutamol blocked these changes in protein expression and muscle mechanics. Chronic stimulation of latissimus dorsi decreased the levels of the fast-twitch isoform of sarco-/endoplasmic reticulum Ca(2+)-ATPase (SERCA1a) and increased SERCA2a protein expression and decreased calcium uptake rate by muscle homogenates. These changes were blocked by salbutamol. 3. The loss of latissimus dorsi muscle weight by chronic stimulation was partially blocked by salbutamol.

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The canine latissimus dorsi was stimulated at 1 Hz via the thoracodorsal nerve for 70 days. Seven days of muscle stimulation caused muscle mass, fibre cross-sectional areas, and tetanic tensions to decrease. Fourteen days of stimulation produced marked decreases in Ca(2+)-uptake rates in a membrane fraction containing sarcoplasmic reticulum. At this time there was a decline in fusion frequency, but no statistically significant changes in time-to-peak tension, total contraction times, or half-relaxation times. With 42 days of stimulation a switch from the fast-twitch to the slow-twitch phenotype was indicated by elevations in the levels of expression of the slow-twitch isoforms of sarco(endo)plasmic reticulum Ca(2+)-ATPase and myosin heavy chain-I, and increases in half-relaxation times, total contraction times and time-to-peak tensions. Decreases in muscle shortening velocity correlated negatively with increases in myosin heavy chain-I levels. Up-regulation of the slow-twitch isoforms of sarco(endo)plasmic reticulum Ca(2+)-ATPase increases in half-relaxation times. The changes in the slow-twitch isoform of sarco(endo)plasmic reticulum Ca(2+)-ATPase and myosin heavy chain-I levels indicated coordinate expression of these two proteins in chronically stimulated muscles.