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 considera tions suggest that the important factor should be the number of acetylcholi ne receptors (AChR) relative to fibre size. However, this hypothesis could not be verified in the goat because the number of AChR was relatively const ant 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 twitc h after a dose of 15 mu g 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 seve n cats anaesthetized with pentobarbital. CSA of the muscle fibres and numbe r of junctional AChR in these muscles were measured by histological methods and I-125-alpha-bungdrotoxin binding assay, respectively, and the number o f AChR per unit fibre CSA calculated. The association between muscle respon se (ED50 and duration of block) and fibre CSA or number of AChR per unit fi bre CSA was then tested by regression analyses. Duration of block varied be tween the six muscles (mean 8.9 (SEM 2.6) to 20.3 (3.1) min; P = 0.0001) bu t ED50 did not (7.5 (1.5) to 15.6 (2.5) mu g 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 (r(2) = 0.30; P = 0.0002) and the ED50 increased as the number of AChR per fibre CSA increased (r(2) = 0.240; P = 0.0016). These results in the cat suggest that the number of junctional AC hR relative to fibre CSA is a morphological predictor of the differential s ensitivities of muscles to neuromuscular blocking agents.