title: Developmentally delayed sensitivity of acetylcholine receptor in myotubes of nerve-muscle cocultures from genetically diabetic mouse embryos.
abstract: The neuromuscular junctions of genetically diabetic KK-CAy mice are reported to be hypersensitive to succinylcholine (SuCh) but not to d-tubocurarine (d-TC). Spinal cord-muscle cocultures from normal ddY and diabetic KK-CAy mouse embryos were studied to examine the involvement of genetic factors in this hypersensitivity to SuCh. KK-CAy myotubes were morphologically normal, as determined by light microscopy. KK-CAy myotubes showed a progressive increase in the resting membrane potentials and acetylcholine (ACh) sensitivity with development, but this development was delayed when compared with ddY myotubes. The ACh receptor clusters, fluorescently labeled by fluorescein isothiocyanate conjugated alpha-bungarotoxin (FITC-alpha BuTX), were formed on the surface membrane of KK-CAy myotubes. The developmental increase of the total amount of fluorescence within ACh receptor clusters on KK-CAy myotubes was also slower than that of ddY myotubes. Depolarization by SuCh was sustained at a higher level in KK-CAy myotubes. In regards to the inhibition of ACh potentials, KK-CAy myotubes were not hypersensitive to both SuCh and d-TC when compared with ddY myotubes. These results suggest that the hypersensitivity to SuCh is not dependent on the genetic difference between ddY and KK-CAy mice, and is probably due to the developmentally diabetic state of the neuromuscular junction.
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004622:Embryo, Mammalian; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D011950:Receptors, Cholinergic