THE BETA(2)-AGONIST SALBUTAMOL AFFECTS THE EXPRESSION OF PHOSPHOLAMBAN AND BOTH ISOFORMS OF SERCA IN CANINE SKELETAL-MUSCLE AND BLOCKS CHANGES IN THESE INDUCED BY NEUROMUSCULAR STIMULATION

Chronic administration of salbutamol induced expression of hybrid fibe rs in canine skeletal muscles. Fast-twitch fibers expressed SERCA2a (t he slow-twitch isoform of sarcoplasmic reticulum Ca2+-ATPase) and slow -twitch fibers expressed SERCA1 (the fast-twitch isoform of the Ca2+-A TPase). The proportion of fibers that became hybrid increased from a s mall percentage in the control muscles to 30% in the predominantly fas t-twitch latissimus dorsi and to 45% in the predominantly slow-twitch vastus intermedius. In contrast to this response by the SERCA genes th e phospholamban gene response was muscle specific. The fraction of fib ers that expressed phospholamban decreased slightly in the latissimus dorsi while increasing moderately in the vastus intermedius. The effec ts of chronic neurostimulation of the latissimus dorsi on SERCA1, SERC A2a and phospholamban levels were mostly blocked by salbutamol. While 100% of fibers from neurostimulated muscles expressed phospholamban, o nly 51% of the fibers from the neurostimulated and salbutamol-treated muscles expressed it. In the neurostimulated muscle, very few muscle f ibers expressed SERCA1a while 61% of the fibers that received salbutam ol expressed it, albeit as hybrid fibers. The levels of SERCA2a in res ponse to these interventions were just the opposite. In the neurostimu lated muscle 37.5% of fibers were hybrid and 62.5% expressed SERCA2a o nly. With co-administration of neurostimulation and salbutamol, 61.3% of fibers were hybrid and 38.7% expressed SERCA2a only.