Journal of Neuroscience, Vol 9, 884-892, Copyright © 1989 by Society for Neuroscience
Open channel structure and ion binding sites of the nicotinic acetylcholine receptor channel
JA Dani
Baylor College of Medicine, Department of Physiology, Houston, Texas 77030.
Clonal BC3H-1 muscle cells were studied using patch-clamp techniques. The
structure and ion binding sites of the nicotinic ACh receptor channel were
examined by measuring permeability ratios and streaming potentials. The
permeability ratio of lithium to ammonium remained constant from 10 to 150
mM. That result indicates there is one primary binding site in the
narrowest region of the channel over the concentration range tested. There
are, however, other binding sites and many ions in the large entrance
vestibules. The sites in the wider regions of the channel influence ionic
permeation, but the main determinant of transport is the site directly in
the permeation pathway. An estimate of the length of the narrow region was
obtained from streaming potential measurements. The streaming potential is
directly related to the number of water molecules coupled to the transport
of a permeant ion through the pore. Under proper experimental conditions,
streaming potential measurements indicated that the narrowest cross section
of the pore holds only about 6 water molecules. Therefore, the narrowest
cross section is very short, and it contains one main binding site. The
overall results are consistent with the pore being lined by transmembrane
helices with a low charge density. Since the open pore has a short narrow
region, the helices that rim the pore may spread out from the narrowest
cross section. The widening of the pore would expose a second set of
transmembrane helices at the interstices between the first set of helices.
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