Salbutamol changes the molecular and mechanical properties of canine skeletal muscle.
1. Salbutamol, a beta 2-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 Ca(2+)-ATPase (SERCA2a) and phospholamban proteins, and increased the level of the fast-twitch isoform of sarco-/endoplasmic reticulum Ca(2+)-ATPase (SERCA1a). 2. Changes in the levels of SERCA proteins, particularly SERCA1a, 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 SERCA1a, 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 change in the level of HC-I isoform.
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0551, USA.
K M
KM
Zhang
P
P
Hu
S W
SW
Wang
J J
JJ
Feher
L D
LD
Wright
A S
AS
Wechsler
J A
JA
Spratt
F N
FN
Briggs
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis; D004285:Dogs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D000099211:Phospholamban
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000420:Albuterol; D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D009124:Muscle Proteins; D018995:Myosin Heavy Chains; D012333:RNA, Messenger; D000099211:Phospholamban