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Published November 1, 1990 | Published
Journal Article Open

Acetylcholine Receptor Clustering is Triggered by a Change in the Density of a Nonreceptor Molecule

Abstract

Acetylcholine receptors become clustered at the neuromuscular junction during synaptogenesis, at least in part via lateral migration of diffusely expressed receptors. We have shown previously that electric fields initiate a specific receptor clustering event which is dependent on lateral migration in aneural muscle cell cultures (Stollberg, J., and S. E. Fraser. 1988. J. Cell Biol. 107:1397-1408). Subsequent work with this model system ruled out the possibility that the clustering event was triggered by increasing the receptor density beyond a critical threshold (Stollberg, J., and S. E. Fraser. 1990. J. Neurosci. 10:247-255). This leaves two possibilities: the clustering event could be triggered by the field-induced change in the density of some other molecule, or by a membrane voltage-sensitive mechanism (e.g., a voltage-gated calcium signal). Electromigration is a slow, linear process, while voltage-sensitive mechanisms respond in a rapid, nonlinear fashion. Because of this the two possibilities make different predictions about receptor clustering behavior in response to pulsed or alternating electric fields. In the present work we have studied subcellular calcium distributions, as well as receptor clustering, in response to such fields. Subcellular calcium distributions were quantified and found to be consistent with the predicted nonlinear response. Receptor clustering, however, behaves in accordance with the predictions of a linear response, consistent with the electromigration hypothesis. The experiments demonstrate that a local increase in calcium, or, more generally, a voltage-sensitive mechanism, is not sufficient and probably not necessary to trigger receptor clustering. Experiments with slowly alternating electric fields confirm the view that the clustering of acetylcholine receptors is initiated by a local change in the density of some non-receptor molecule.

Additional Information

© 1990 Rockefeller University Press. After the Initial Publication Period, RUP will grant to the public the non- exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode. Received for publication 26 April 1990 and in revised form 8 August 1990. Published November 1, 1990. We thank Arm Faravardeh for technical assistance. This work was supported by a grant from the Monsanto Corporation, and National Institutes of Health grant No. NS26943.

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