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

The effect of the β 2 ‐adrenoceptor agonist, terbutaline, was investigated on simultaneously measured force and intracellular free calcium ([Ca 2+ ] i ) in intact rat soleus muscle fibres, and on contractile protein function and Ca 2+ content of the sarcoplasmic reticulum (SR) in skinned fibres. Terbutaline (10 μ M ) had no significant effect on either resting force or [Ca 2+ ] i . Exposure to terbutaline increased both the integral of the indo‐1 ratio transient and peak twitch force by 37%. 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. Terbutaline increased tetanic force at near maximal stimulation frequencies (50 Hz) by increasing tetanic [Ca 2+ ] i . Force relaxation was accelerated at this frequency with no significant change in the indo‐1 ratio transient decay rate. All of terbutaline's effects on force and indo‐1 ratio transients in intact fibres were completely blocked and reversed by ICI 118551 (1 μ M ). Mechanically skinned fibres isolated from intact muscles pre‐treated with terbutaline showed no significant changes in SR Ca 2+ content, myofilament [Ca 2+ ] i ‐sensitivity or maximum force generating capacity. The results suggest that terbutaline primarily modulates force by altering the amplitude and decay rate of the [Ca 2+ ] 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 β 2 ‐agonists probably reflects individual differences in basal phosphorylation levels of PLB relative to that of RR.British Journal of Pharmacology (1999) 126 , 1717–1724; doi: 10.1038/sj.bjp.0702482