Spontaneous changes in acetylcholine receptor and calcium leakage activity in cell-attached patches from cultured dystrophic myotubes

Document Type

Article

Publication Title

Pflugers Archiv European Journal of Physiology

Abstract

Calcium leakage activity (CLA) was recorded in association with acetylcholine receptor (AChR) activity in cell-attached patches from cultured nondystrophic and dystrophic (mdx) myotubes. Cell-attached recordings from dystrophic myotubes exhibited spontaneous transitions in the activity pattern that were characterized by an instability of AChR function and a decrease in the frequency of AChR events. Recordings from nondystrophic myotubes could be maintained for similar time periods without observing any consistent changes in the distribution of CLA and AChR events, thus indicating that the conditions of the experiment were not conducive to developing AChR instability or desensitization in nondystrophic myotubes. In dystrophic myotubes, the decrease in AChR event frequency was associated with an increase in small-conductance events which had the characteristics of CLA, and the subsequent acquisition of an inside-out patch appeared to restore the AChR activity. Examination of baseline current-voltage relationships indicated that dystrophic and nondystrophic patches exhibited the same general pattern of seal maturation with temporal increases in the total- patch circuit resistance. These results are discussed in relation to the AChR aggregation hypothesis, which proposes that the absence of dystrophin leads to abnormal AChR-cytoskeletal interactions and CLA that can be reversed by removing the influence of intracellular signal transduction enzymes that aggregate and stabilize AChR clusters.

First Page

371

Last Page

380

DOI

10.1007/s004240050791

Publication Date

2-16-1999

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