Morphological correlates of the differential responses of muscles to vecuronium

We have noted previously that duration of vecuronium block correlated with fibre size in six muscle groups in the goat. Electrophysiological considerations suggest that the important factor should be the number of acetylcholine receptors (AChR) relative to fibre size. However, this hypothesis could not be verified in the goat because the number of AChR was relatively constant in the different muscles despite differences in fibre size. Therefore, in this study, we have investigated the relationship between sensitivity to vecuronium, as reflected by the ED50 and duration of block, of six muscles in the cat and the number of AChR per unit fibre cross-sectional area (CSA). The ED50 and duration of action (time to 50% recovery of the first twitch after a dose of 15 micrograms kg-1) of vecuronium in the tibialis cranialis, soleus, rectus abdominis, masseter, diaphragm and thyroarytenoideus muscles were determined during train-of-four stimulation and EMG recording in seven cats anaesthetized with pentobarbital. CSA of the muscle fibres and number of junctional AChR in these muscles were measured by histological methods and 125I-alpha-bungarotoxin binding assay, respectively, and the number of AChR per unit fibre CSA calculated. The association between muscle response (ED50 and duration of block) and fibre CSA or number of AChR per unit fibre CSA was then tested by regression analyses. Duration of block varied between the six muscles (mean 8.9 (SEM 2.6) to 20.3 (3.1) min; P = 0.0001) but ED50 did not (7.5 (1.5) to 15.6 (2.5) micrograms kg-1; P = 0.185). Fibre CSA and number of AChR per unit fibre CSA also varied between these muscles (P = 0.0001). Duration to 50% TI recovery was prolonged in muscles with a low number of AChR relative to fibre CSA (r2 = 0.30; P = 0.0002) and the ED50 increased as the number of AChR per fibre CSA increased (r2 = 0.240; P = 0.0016). These results in the cat suggest that the number of junctional AChR relative to fibre CSA is a morphological predictor of the differential sensitivities of muscles to neuromuscular blocking agents.