HYPERSENSITIVITY OF ACETYLCHOLINE RECEPTOR IN DIABETIC SKELETAL MUSCLE TO NEUROMUSCULAR BLOCKERS : THE EFFECT ON MYOTUBES CULTURED WITH SPINAL CORD OR ITS EXTRACT

The hypersensitivity of the neuromuscular junctions of diabetic mice to succinyl-choline (SuCh), but not to d-tubocurarine (d-TC), was investigated using a cross culture preparation of diabetic skeletal muscle or spinal cord extract with normal tissues. Whether the hypersensitivity is due to the muscle cells themselves was examined using adult muscle of diabetic KK-CAy, prediabetic KK-CAy and normal ddY mice cocultured with embryonic spinal cord of normal ddY mice. The cultured neuromuscular junctions between diabetic KK-CAy muscle and normal ddY spinal cord was hypersensitive to SuCh, but not to d-TC. In contrast, such junctions between prediabetic KK-CAy muscle and normal ddY spinal cord were not hypersensitive to either drug. The involvement of neuronal factors in hypersensitivity to SuCh in diabetic KK-CAy neuromuscular junctions was examined using adult spinal cord extract (SCE) from diabetic KK-CAy and from normal ddY mice. We followed the time course of change in sensitivity of the acetylcholine (ACh) receptors in normal ddY embryonic myotubes to SuCh and d-TC. Both diabetic SCE and normal SCE reduced the sensitivity of myotubes to ACh ; the reduction of ACh potential amplitudes by the former was less than that by the latter. Myotubes cultured with diabetic SCE was hypersensitive to both 1.51 μM SuCh and 0.134 μM d-TC. These results suggest that the hypersensitivity of the neuromuscular junctions in diabetic KK-CAy mice to SuCh but not to d-TC is mainly attributable to the diabetic muscle cells. themselves.