Effects of terbutaline on force and intracellular calcium in slow-twitch skeletal muscle fibres of the rat

1 The effect of the beta(2)-adrenoceptor agonist, terbutaline, was investigated on simultaneously measured force and intracellular free calcium ([Ca2+](i)) in intact rat soleus muscle fibres, and on contractile protein function and Ca2+ content of the sarcoplasmic reticulum (SR) in skinned fibres. 2 Terbutaline (10 mu M) had no significant effect on either resting force or [Ca2+](i). Exposure to terbutaline increased both the integral of the indo-1 ratio transient and peak twitch force by 37%. 3 At sub-maximal (10 Hz) stimulation frequencies, terbutaline accelerated force relaxation but had highly variable effects on tetanic force amplitude. The corresponding indo-1 ratio transients were significantly larger, and faster to decay than the controls. 4 Terbutaline increased tetanic force at near maximal stimulation frequencies (50 Hz) by increasing tetanic [Ca2+](i). Force relaxation was accelerated at this frequency with no significant change in the indo-1 ratio transient decay rate. 5 All of terbutaline's effects on force and indo-1 ratio transients in intact fibres were completely blocked and reversed by ICI 118551 (1 mu M). 6 Mechanically skinned fibres isolated from intact muscles pre-treated with terbutaline showed no significant changes in SR Ca2+ content, myofilament [Ca2+](i)-sensitivity or maximum force generating capacity. 7 The results suggest that terbutaline primarily modulates force by altering the amplitude and decay rate of the [Ca2+](i) transient via phosphorylation of both the ryanodine receptor (RR) and the SR pump regulatory protein, phospholamban (PLB). The high variability of responses of slow-twitch muscles to beta(2)-agonists probably reflects individual differences in basal phosphorylation levels of PLB relative to that of RR.