The selectivity of the channel coupled to the 5-HT3 receptor.
The 5-HT3 receptor is unusual among receptors for biogenic amines in that it is directly coupled to an ion channel that is highly permeable to Na+ and K+. We have studied the permeation properties of this channel in order to achieve a more detailed understanding of its physiological function and to extend the comparison with other ligand gated channels. The 5-HT3 receptor channel is significantly permeable to the organic cations Tris, choline, and N-methyl-glucamine, with permeabilities decreasing with size. The permeability ratios for Tris and choline are similar to those determined for the nicotinic receptor; the permeability ratio for Tris is also similar to that of a non-N-methyl-D-aspartate (non-NMDA) excitatory amino acid receptor. This suggests that the diameters at the narrowest parts of these 3 channels are similar. The Ca2+ permeability of the 5-HT3 receptor channel is relatively low, with an upper bound to PCa/PNa estimated as 0.076. The single channel conductance, as determined by noise analysis, was also relatively low, with a value of 4.4 +/- 0.5 pS. Thus, both the Ca2+ permeability and single channel conductance are lower than those of the nicotinic receptor. In these respects, the 5-HT3 receptor is closer to non-NMDA excitatory amino acid receptors. These results are interpreted in terms of a model of the 5-HT3 receptor channel in which the interior has a lower polarizability, and possibly a greater length, in comparison with the nicotinic acetylcholine receptor channel.
Yakel
J L
JL
Department of Physiology, University of Wisconsin-Madison, School of Medicine 53706.
Shao
X M
XM
Jackson
M B
MB
D002413:Cations, Divalent / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D010539:Permeability; D011188:Potassium / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D013329:Structure-Activity Relationship
D002413:Cations, Divalent; D002712:Chlorides; D007473:Ion Channels; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; D012964:Sodium; D011188:Potassium