Rapid lateral diffusion of functional ACh receptors in embryonic muscle cell membrane

Abstract

During synaptogenesis of the skeletal neuromuscular junction, the acetylcholine (ACh) receptors dispersed over the surface of the embryonic muscle become highly concentrated at the subsynaptic membrane^1,2. The mechanism by which a nerve induces such a modulation of ACh receptor topography is unknown. Of various possibilities³, the simplest explanation is that the ACh receptors, freely diffusing in the plane of the muscle membrane, are trapped at the site of nerve contact^4,5. This ‘diffusion-trap’ mechanism is plausible only if the diffusion distance covered by the ACh receptors within its lifetime on the cell surface is at least comparable with the dimension of the embryonic muscle fibre (see also discussion in ref. 1). Photo-bleaching studies had suggested that this was not the case. In the present study, an electrophysiological method was used to measure the lateral diffusion of the dispersed, functional ACh receptors in the plasma membrane of cultured Xenopus embryonic muscle cells. The results suggest that these ACh receptors undergo rapid lateral diffusion with a diffusion coefficient of 2.6 × 10⁻⁹ cm² s⁻¹ at 22 °C. This rapid diffusion of the dispersed ACh receptors strongly supports a passive diffusion-trap mechanism for the localization of ACh receptors at the site of nerve–muscle contact.