SINGLE-CHANNEL EVIDENCE FOR A CYTOSKELETAL DEFECT INVOLVING ACETYLCHOLINE-RECEPTORS AND CALCIUM INFLUX IN CULTURED DYSTROPHIC (MDX) MYOTUBES

Single channel events that exhibited the conductance, event duration, and ion selectivity characteristics of calcium leakage activity (CLA) were recorded in association with acetylcholine receptor (AChR) activi ty in cultured nondystrophic myotubes. The CLA was observed in the pre sence or absence of acetylcholine (ACh), and at normal or elevated con centrations of calcium. In contrast to results from nondystrophic myot ubes, cell-attached patches from several cultured dystrophic (mdx) myo tubes exhibited 100% CLA with no AChR activity, even though ACh was pr esent in the pipette solution, Acquisition of an inside-out patch from these membrane areas produced a profound decrease in CLA and the appe arance of AChR events exhibiting typical conductance and event duratio n characteristics. These results suggest that CLA in dystrophic muscle is produced, in part, by unusual physical interactions between AChRs and the dystrophic cytoskeleton that are mediated by the action of int racellular modulators responsible for aggregating and stabilizing AChR s. (C) 1996 John Wiley & Sons, Inc.